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ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen

Najnin, Rifat Ara Al Mahmud, Md Rasel Rahman, Md Maminur Takeda, Shunichi Sasanuma, Hiroyuki Tanaka, Hisashi Murakawa, Yasuhiro Shimizu, Naoto Akter, Salma Takagi, Masatoshi Sunada, Takuro Akamatsu, Shusuke He, Gang Itou, Junji Toi, Masakazu Miyaji, Mary Tsutsui, Kimiko M. Keeney, Scott Yamada, Shintaro 京都大学 DOI:10.1016/j.celrep.2022.111909

2023.01.31

概要

ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens. This response depends on topoisomerase II (TOP2), which generates TOP2-DNA double-strand break (DSB) complexes and rejoins the breaks. When TOP2-mediated ligation fails, ATM facilitates DSB repair. After estrogen exposure, TOP2-dependent DSBs arise at the c-MYC enhancer in human BC cells, and their defective repair changes the activation profile of enhancers and induces the overexpression of many genes, including the c-MYC oncogene. CRISPR/Cas9 cleavage at the enhancer also causes c-MYC overexpression, indicating that this DSB causes c-MYC overexpression. Estrogen treatment induced c-Myc protein overexpression in mammary epithelial cells of ATM-deficient mice. In conclusion, ATM suppresses the c-Myc-driven proliferative effects of estrogens, possibly explaining such tissue-specific oncogenesis.

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参考文献

1. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., and Je- mal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 68, 394–424. https://doi.org/10.3322/caac.21492.

2. Kohler, B.A., Sherman, R.L., Howlader, N., Jemal, A., Ryerson, A.B., Henry, K.A., Boscoe, F.P., Cronin, K.A., Lake, A., Noone, A.M., et al. (2015). Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J. Natl. Cancer Inst. 107, djv048. https://doi.org/10.1093/jnci/ djv048.

3. Momozawa, Y., Iwasaki, Y., Parsons, M.T., Kamatani, Y., Takahashi, A., Tamura, C., Katagiri, T., Yoshida, T., Nakamura, S., Sugano, K., et al. (2018). Germline pathogenic variants of 11 breast cancer genes in 7, 051 Japanese patients and 11, 241 controls. Nat. Commun. 9, 4083. https://doi.org/10.1038/s41467-018-06581-8.

4. Huang, K.-l., Mashl, R.J., Wu, Y., Ritter, D.I., Wang, J., Oh, C., Paczkow- ska, M., Reynolds, S., Wyczalkowski, M.A., Oak, N., et al. (2018). Patho- genic germline variants in 10, 389 adult cancers. Cell 173, 355–370.e14.

5. Angeli, D., Salvi, S., and Tedaldi, G. (2020). Genetic predisposition to breast and ovarian cancers: how many and which genes to test? Int. J. Mol. Sci. 21, 1128.

6. Breast Cancer Association Consortium; Dorling, L., Carvalho, S., Allen, J., Gonza´ lez-Neira, A., Luccarini, C., Wahlstro¨ m, C., Pooley, K.A., Par- sons, M.T., Fortuno, C., Wang, Q., et al. (2021). Breast cancer risk genes - association analysis in more than 113, 000 women. N. Engl. J. Med. 384, 428–439. https://doi.org/10.1056/NEJMoa1913948.

7. Broeks, A., Urbanus, J.H., Floore, A.N., Dahler, E.C., Klijn, J.G., Rutgers, E.J., Devilee, P., Russell, N.S., van Leeuwen, F.E., and van ’t Veer, L.J. (2000). ATM-heterozygous germline mutations contribute to breast can- cer-susceptibility. Am. J. Hum. Genet. 66, 494–500. https://doi.org/10. 1086/302746.

8. Renwick, A., Thompson, D., Seal, S., Kelly, P., Chagtai, T., Ahmed, M., North, B., Jayatilake, H., Barfoot, R., Spanova, K., et al. (2006). ATM mu- tations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat. Genet. 38, 873–875.

9. Tavtigian, S.V., Oefner, P.J., Babikyan, D., Hartmann, A., Healey, S., Le Calvez-Kelm, F., Lesueur, F., Byrnes, G.B., Chuang, S.-C., Forey, N., et al. (2009). Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. Am. J. Hum. Genet. 85, 427–446.

10. Renault, A.L., Mebirouk, N., Fuhrmann, L., Bataillon, G., Cavaciuti, E., Le Gal, D., Girard, E., Popova, T., La Rosa, P., Beauvallet, J., et al. (2018). Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers. Breast Cancer Res. 20, 28. https:// doi.org/10.1186/s13058-018-0951-9.

11. Thompson, D., Duedal, S., Kirner, J., McGuffog, L., Last, J., Reiman, A., Byrd, P., Taylor, M., and Easton, D.F. (2005). Cancer risks and mortality in heterozygous ATM mutation carriers. J. Natl. Cancer Inst. 97, 813–822. https://doi.org/10.1093/jnci/dji141.

12. Bakkenist, C.J., and Kastan, M.B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Na- ture 421, 499–506. https://doi.org/10.1038/nature01368.

13. Banin, S., Moyal, L., Shieh, S., Taya, Y., Anderson, C.W., Chessa, L., Smorodinsky, N.I., Prives, C., Reiss, Y., Shiloh, Y., and Ziv, Y. (1998). Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281, 1674–1677. https://doi.org/10.1126/science.281. 5383.1674.

14. Vousden, K.H., and Lu, X. (2002). Live or let die: the cell’s response to p53. Nat. Rev. Cancer 2, 594–604.

15. Lee, J.H., and Paull, T.T. (2021). Cellular functions of the protein kinase ATM and their relevance to human disease. Nat. Rev. Mol. Cell Biol. 22, 796–814. https://doi.org/10.1038/s41580-021-00394-2.

16. Escribano-Dı´az, C., Orthwein, A., Fradet-Turcotte, A., Xing, M., Young, J.T.F., Tka´ cˇ, J., Cook, M.A., Rosebrock, A.P., Munro, M., Canny, M.D., et al. (2013). A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol. Cell 49, 872–883. https://doi.org/10.1016/j.molcel.2013.01.001.

17. You, Z., Shi, L.Z., Zhu, Q., Wu, P., Zhang, Y.W., Basilio, A., Tonnu, N., Verma, I.M., Berns, M.W., and Hunter, T. (2009). CtIP links DNA dou- ble-strand break sensing to resection. Mol. Cell 36, 954–969. https:// doi.org/10.1016/j.molcel.2009.12.002.

18. Nakamura, K., Kustatscher, G., Alabert, C., Ho¨ dl, M., Forne, I., Vo¨ lker-Al- bert, M., Satpathy, S., Beyer, T.E., Mailand, N., Choudhary, C., et al. (2021). Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination. Mol. Cell 81, 1084–1099.e6. https://doi.org/10.1016/j. molcel.2020.12.025.

19. Balmus, G., Pilger, D., Coates, J., Demir, M., Sczaniecka-Clift, M., Bar- ros, A.C., Woods, M., Fu, B., Yang, F., Chen, E., et al. (2019). ATM orchestrates the DNA-damage response to counter toxic non-homolo- gous end-joining at broken replication forks. Nat. Commun. 10, 87. https://doi.org/10.1038/s41467-018-07729-2.

20. Liang, J., and Shang, Y. (2013). Estrogen and cancer. Annu. Rev. Physiol. 75, 225–240.

21. La Vignera, S., Condorelli, R.A., Russo, G.I., Morgia, G., and Calogero, A.E. (2016). Endocrine control of benign prostatic hyperplasia. Andrology 4, 404–411.

22. Bondesson, M., Hao, R., Lin, C.Y., Williams, C., and Gustafsson, J.A˚ . (2015). Estrogen receptor signaling during vertebrate development. Bio- chim. Biophys. Acta 1849, 142–151. https://doi.org/10.1016/j.bbagrm. 2014.06.005.

23. Matutino, A., Joy, A.A., Brezden-Masley, C., Chia, S., and Verma, S. (2018). Hormone receptor-positive, HER2-negative metastatic breast cancer: redrawing the lines. Curr. Oncol. 25, S131–S141. https://doi. org/10.3747/co.25.4000.

24. Kokontis, J., Takakura, K., Hay, N., and Liao, S. (1994). Increased androgen receptor activity and altered c-myc expression in prostate can- cer cells after long-term androgen deprivation. Cancer Res. 54, 1566–1573.

25. Shang, Y., Hu, X., DiRenzo, J., Lazar, M.A., and Brown, M. (2000). Cofactor dynamics and sufficiency in estrogen receptor–regulated tran- scription. Cell 103, 843–852.

26. Wang, C., Mayer, J.A., Mazumdar, A., Fertuck, K., Kim, H., Brown, M., and Brown, P.H. (2011). Estrogen induces c-myc gene expression via an upstream enhancer activated by the estrogen receptor and the AP-1 transcription factor. Mol. Endocrinol. 25, 1527–1538.

27. Yang, H., Liu, T., Wang, J., Li, T.W.H., Fan, W., Peng, H., Krishnan, A., Gores, G.J., Mato, J.M., and Lu, S.C. (2016). Deregulated methionine ad- enosyltransferase a1, c-Myc, and Maf proteins together promote cholan- giocarcinoma growth in mice and humans. Hepatology 64, 439–455.

28. Fulco, C.P., Munschauer, M., Anyoha, R., Munson, G., Grossman, S.R., Perez, E.M., Kane, M., Cleary, B., Lander, E.S., and Engreitz, J.M. (2016). Systematic mapping of functional enhancer-promoter connections with CRISPR interference. Science 354, 769–773. https://doi.org/10.1126/ science.aag2445.

29. Hnisz, D., Abraham, B.J., Lee, T.I., Lau, A., Saint-Andre´ , V., Sigova, A.A., Hoke, H.A., and Young, R.A. (2013). Super-enhancers in the control of cell identity and disease. Cell 155, 934–947. https://doi.org/10.1016/j. cell.2013.09.053.

30. Love´ n, J., Hoke, H.A., Lin, C.Y., Lau, A., Orlando, D.A., Vakoc, C.R., Bradner, J.E., Lee, T.I., and Young, R.A. (2013). Selective inhibition of tu- mor oncogenes by disruption of super-enhancers. Cell 153, 320–334. https://doi.org/10.1016/j.cell.2013.03.036.

31. Lin, C.Y., Love´ n, J., Rahl, P.B., Paranal, R.M., Burge, C.B., Bradner, J.E., Lee, T.I., and Young, R.A. (2012). Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151, 56–67.

32. Nie, Z., Hu, G., Wei, G., Cui, K., Yamane, A., Resch, W., Wang, R., Green, D.R., Tessarollo, L., Casellas, R., et al. (2012). c-Myc is a universal ampli- fier of expressed genes in lymphocytes and embryonic stem cells. Cell 151, 68–79.

33. Schaub, F.X., Dhankani, V., Berger, A.C., Trivedi, M., Richardson, A.B., Shaw, R., Zhao, W., Zhang, X., Ventura, A., Liu, Y., et al. (2018). Pan-can- cer alterations of the MYC oncogene and its proximal network across the cancer genome atlas. Cell Syst. 6, 282–300.e2. https://doi.org/10.1016/j. cels.2018.03.003.

34. Dave, K., Sur, I., Yan, J., Zhang, J., Kaasinen, E., Zhong, F., Blaas, L., Li, X., Kharazi, S., Gustafsson, C., et al. (2017). Mice deficient of. Elife 6, e23382. https://doi.org/10.7554/eLife.23382.

35. Austin, C.A., Lee, K.C., Swan, R.L., Khazeem, M.M., Manville, C.M., Crid- land, P., Treumann, A., Porter, A., Morris, N.J., and Cowell, I.G. (2018). TOP2B: the first thirty years. Int. J. Mol. Sci. 19, 2765. https://doi.org/ 10.3390/ijms19092765.

36. Madabhushi, R. (2018). The roles of DNA topoisomerase IIb in transcrip- tion. Int. J. Mol. Sci. 19, 1917.

37. McNamara, S., Wang, H., Hanna, N., and Miller, W.H. (2008). Topoisom- erase IIb negatively modulates retinoic acid receptor a function: a novel mechanism of retinoic acid resistance. Mol. Cell Biol. 28, 2066–2077.

38. Haffner, M.C., Aryee, M.J., Toubaji, A., Esopi, D.M., Albadine, R., Gurel, B., Isaacs, W.B., Bova, G.S., Liu, W., Xu, J., et al. (2010). Androgen- induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nat. Genet. 42, 668–675.

39. Wong, R.H.F., Chang, I., Hudak, C.S.S., Hyun, S., Kwan, H.-Y., and Sul, H.S. (2009). A role of DNA-PK for the metabolic gene regulation in response to insulin. Cell 136, 1056–1072. https://doi.org/10.1016/j.cell. 2008.12.040.

40. Trotter, K.W., King, H.A., and Archer, T.K. (2015). Glucocorticoid recep- tor transcriptional activation via the BRG1-dependent recruitment of TOP2 beta and ku70/86. Mol. Cell Biol. 35, 2799–2817. https://doi.org/ 10.1128/mcb.00230-15.

41. Bunch, H., Lawney, B.P., Lin, Y.-F., Asaithamby, A., Murshid, A., Wang, Y.E., Chen, B.P.C., and Calderwood, S.K. (2015). Transcriptional elonga- tion requires DNA break-induced signalling. Nat. Commun. 6, 10191.

42. Dellino, G.I., Palluzzi, F., Chiariello, A.M., Piccioni, R., Bianco, S., Furia, L., De Conti, G., Bouwman, B.A.M., Melloni, G., Guido, D., et al. (2019). Release of paused RNA polymerase II at specific loci favors DNA dou- ble-strand-break formation and promotes cancer translocations. Nat. Genet. 51, 1011–1023. https://doi.org/10.1038/s41588-019-0421-z.

43. Manville, C.M., Smith, K., Sondka, Z., Rance, H., Cockell, S., Cowell, I.G., Lee, K.C., Morris, N.J., Padget, K., Jackson, G.H., and Austin, C.A. (2015). Genome-wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells. Biol. Open 4, 1436–1447. https://doi.org/10.1242/bio.014308.

44. Pommier, Y., Sun, Y., Huang, S.-y.N., and Nitiss, J.L. (2016). Roles of eu- karyotic topoisomerases in transcription, replication and genomic stabil- ity. Nat. Rev. Mol. Cell Biol. 17, 703–721. https://doi.org/10.1038/nrm. 2016.111.

45. Pommier, Y., Nussenzweig, A., Takeda, S., and Austin, C. (2022). Human topoisomerases and their roles in genome stability and organization. Nat. Rev. Mol. Cell Biol. 23, 407–427. https://doi.org/10.1038/s41580-022- 00452-3.

46. Nitiss, J.L. (2009). Targeting DNA topoisomerase II in cancer chemo- therapy. Nat. Rev. Cancer 9, 338–350.

47. Gale, K.C., and Osheroff, N. (1992). Intrinsic intermolecular DNA ligation activity of eukaryotic topoisomerase II. Potential roles in recombination. J. Biol. Chem. 267, 12090–12097.

48. Go´ mez-Herreros, F., Schuurs-Hoeijmakers, J.H.M., McCormack, M., Greally, M.T., Rulten, S., Romero-Granados, R., Counihan, T.J., Chaila, E., Conroy, J., Ennis, S., et al. (2014). TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural func- tion. Nat. Genet. 46, 516–521.

49. Hoa, N.N., Shimizu, T., Zhou, Z.W., Wang, Z.Q., Deshpande, R.A., Paull, T.T., Akter, S., Tsuda, M., Furuta, R., Tsutsui, K., et al. (2016). Mre11 is essential for the removal of lethal topoisomerase 2 covalent cleavage complexes (vol 64, pg 580, 2016). Mol. Cell 64, 1010. https://doi.org/ 10.1016/j.molcel.2016.11.028.

50. Tubbs, A., and Nussenzweig, A. (2017). Endogenous DNA damage as a source of genomic instability in cancer. Cell 168, 644–656. https://doi. org/10.1016/j.cell.2017.01.002.

51. Morimoto, S., Tsuda, M., Bunch, H., Sasanuma, H., Austin, C., and Takeda, S. (2019). Type II DNA topoisomerases cause spontaneous dou- ble-strand breaks in genomic DNA. Genes 10, 868. https://doi.org/10. 3390/genes10110868.

52. Pommier, Y., and Marchand, C. (2012). Interfacial inhibitors: targeting macromolecular complexes (vol 11, pg 25, 2012). Nat. Rev. Drug Discov. 11, 250, 233. https://doi.org/10.1038/nrd3665.

53. Akagawa, R., Trinh, H.T., Saha, L.K., Tsuda, M., Hirota, K., Yamada, S., Shibata, A., Kanemaki, M.T., Nakada, S., Takeda, S., and Sasanuma, H. (2020). UBC13-Mediated ubiquitin signaling promotes removal of block- ing adducts from DNA double-strand breaks. iScience 23, 101027. https://doi.org/10.1016/j.isci.2020.101027.

54. Go´ mez-Herreros, F., Romero-Granados, R., Zeng, Z., Alvarez-Quilo´ n, A., Quintero, C., Ju, L., Umans, L., Vermeire, L., Huylebroeck, D., Caldecott, K.W., and Corte´ s-Ledesma, F. (2013). TDP2-Dependent non-homolo- gous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo. PLoS Genet. 9, e1003226. https://doi.org/10.1371/journal.pgen.1003226.

55. Cortes Ledesma, F., El Khamisy, S.F., Zuma, M.C., Osborn, K., and Cal- decott, K.W. (2009). A human 5 ’-tyrosyl DNA phosphodiesterase that re- pairs topoisomerase-mediated DNA damage. Nature 461, 674–678. https://doi.org/10.1038/nature08444.

56. Lee, K.C., Padget, K., Curtis, H., Cowell, I.G., Moiani, D., Sondka, Z., Morris, N.J., Jackson, G.H., Cockell, S.J., Tainer, J.A., and Austin, C.A. (2012). MRE11 facilitates the removal of human topoisomerase II com- plexes from genomic DNA. Biol. Open 1, 863–873. https://doi.org/10. 1242/bio.20121834.

57. Deshpande, R.A., Lee, J.H., Arora, S., and Paull, T.T. (2016). Nbs1 con- verts the human mre11/rad50 nuclease complex into an endo/exonu- clease machine specific for protein-DNA adducts. Mol. Cell 64, 593–606. https://doi.org/10.1016/j.molcel.2016.10.010.

58. Paull, T.T. (2018). 20 years of Mre11 biology: no end in sight. Mol. Cell 71, 419–427.

59. Quennet, V., Beucher, A., Barton, O., Takeda, S., and Lo¨ brich, M. (2011). CtIP and MRN promote non-homologous end-joining of etoposide- induced DNA double-strand breaks in G1. Nucleic Acids Res. 39, 2144–2152. https://doi.org/10.1093/nar/gkq1175.

60. Sasanuma, H., Tsuda, M., Morimoto, S., Saha, L.K., Rahman, M.M., Kiyooka, Y., Fujiike, H., Cherniack, A.D., Itou, J., Callen Moreu, E., et al. (2018). BRCA1 ensures genome integrity by eliminating estrogen- induced pathological topoisomerase II–DNA complexes. Proc. Natl. Acad. Sci. USA. 115, E10642–E10651.

61. Bunting, S.F., Calle´ n, E., Wong, N., Chen, H.T., Polato, F., Gunn, A., Bothmer, A., Feldhahn, N., Fernandez-Capetillo, O., Cao, L., et al. (2010). 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141, 243–254. https:// doi.org/10.1016/j.cell.2010.03.012.

62. Callen, E., Zong, D., Wu, W., Wong, N., Stanlie, A., Ishikawa, M., Pavani, R., Dumitrache, L.C., Byrum, A.K., Mendez-Dorantes, C., et al. (2020). 53BP1 enforces distinct pre- and post-resection blocks on homologous recombination. Mol. Cell 77, 26–38.e7. https://doi.org/10.1016/j.molcel. 2019.09.024.

63. Lange, J., Yamada, S., Tischfield, S.E., Pan, J., Kim, S., Zhu, X., Socci, N.D., Jasin, M., and Keeney, S. (2016). The landscape of mouse meiotic double-strand break formation, processing, and repair. Cell 167, 695– 708.e16. https://doi.org/10.1016/j.cell.2016.09.035.

64. Makharashvili, N., Tubbs, A.T., Yang, S.H., Wang, H., Barton, O., Zhou, Y., Deshpande, R.A., Lee, J.H., Lobrich, M., Sleckman, B.P., et al. (2014). Catalytic and noncatalytic roles of the CtIP endonuclease in dou- ble-strand break end resection. Mol. Cell 54, 1022–1033. https://doi.org/ 10.1016/j.molcel.2014.04.011.

65. Paiano, J., Wu, W., Yamada, S., Sciascia, N., Callen, E., Paola Cotrim, A., Deshpande, R.A., Maman, Y., Day, A., Paull, T.T., and Nussenzweig, A. (2020). ATM and PRDM9 regulate SPO11-bound recombination interme- diates during meiosis. Nat. Commun. 11, 857. https://doi.org/10.1038/ s41467-020-14654-w.

66. Yamada, S., Hinch, A.G., Kamido, H., Zhang, Y., Edelmann, W., and Keeney, S. (2020). Molecular structures and mechanisms of DNA break processing in mouse meiosis. Genes Dev. 34, 806–818. https://doi.org/ 10.1101/gad.336032.119.

67. Wang, H., Yang, H., Shivalila, C.S., Dawlaty, M.M., Cheng, A.W., Zhang, F., and Jaenisch, R. (2013). One-step generation of mice carrying muta- tions in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910–918. https://doi.org/10.1016/j.cell.2013.04.025.

68. A´ lvarez-Quilo´ n, A., Serrano-Benı´tez, A., Lieberman, J.A., Quintero, C., Sa´ nchez-Gutie´ rrez, D., Escudero, L.M., and Corte´ s-Ledesma, F. (2014). ATM specifically mediates repair of double-strand breaks with blocked DNA ends. Nat. Commun. 5, 3347. https://doi.org/10.1038/ ncomms4347.

69. Caldecott, K.W., Ward, M.E., and Nussenzweig, A. (2022). The threat of programmed DNA damage to neuronal genome integrity and plasticity. Nat. Genet. 54, 115–120. https://doi.org/10.1038/s41588-021-01001-y.

70. Ju, B.-G., Lunyak, V.V., Perissi, V., Garcia-Bassets, I., Rose, D.W., Glass, C.K., and Rosenfeld, M.G. (2006). A topoisomerase IIß-mediated dsDNA break required for regulated transcription. science 312, 1798–1802.

71. Williamson, L.M., and Lees-Miller, S.P. (2011). Estrogen receptor alpha- mediated transcription induces cell cycle-dependent DNA double-strand breaks. Carcinogenesis 32, 279–285. https://doi.org/10.1093/carcin/ bgq255.

72. ENCODE Project Consortium; Snyder, M.P., Gingeras, T.R., Moore, J.E., Weng, Z., Gerstein, M.B., Ren, B., Hardison, R.C., Stamatoyannopoulos, J.A., Graveley, B.R., Feingold, E.A., et al. (2020). Perspectives on ENCODE. Nature 583, 693–698. https://doi.org/10.1038/s41586-020- 2449-8.

73. Li, W., Notani, D., Ma, Q., Tanasa, B., Nunez, E., Chen, A.Y., Merkurjev, D., Zhang, J., Ohgi, K., Song, X., et al. (2013). Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Na- ture 498, 516–520. https://doi.org/10.1038/nature12210.

74. FANTOM Consortium and the RIKEN PMI and CLST DGT; Forrest, A.R.R., Kawaji, H., Rehli, M., Baillie, J.K., de Hoon, M.J.L., Haberle, V., Lassmann, T., Kulakovskiy, I.V., Lizio, M., Itoh, M., et al. (2014). A pro- moter-level mammalian expression atlas. Nature 507, 462–470. https:// doi.org/10.1038/nature13182.

75. Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., Suzuki, T., et al. (2014). An atlas of active enhancers across human cell types and tissues. Nature 507, 455–461. https://doi.org/10.1038/nature12787.

76. Hirabayashi, S., Bhagat, S., Matsuki, Y., Takegami, Y., Uehata, T., Kane- maru, A., Itoh, M., Shirakawa, K., Takaori-Kondo, A., Takeuchi, O., et al. (2019). NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements. Nat. Genet. 51, 1369–1379. https://doi.org/10.1038/s41588-019-0485-9.

77. Kristja´ nsdo´ ttir, K., Dziubek, A., Kang, H.M., and Kwak, H. (2020). Popu- lation-scale study of eRNA transcription reveals bipartite functional enhancer architecture. Nat. Commun. 11, 5963. https://doi.org/10. 1038/s41467-020-19829-z.

78. Oh, S., Shao, J., Mitra, J., Xiong, F., D’Antonio, M., Wang, R., Garcia- Bassets, I., Ma, Q., Zhu, X., Lee, J.H., et al. (2021). Enhancer release and retargeting activates disease-susceptibility genes. Nature 595, 735–740. https://doi.org/10.1038/s41586-021-03577-1.

79. Shiraki, T., Kondo, S., Katayama, S., Waki, K., Kasukawa, T., Kawaji, H., Kodzius, R., Watahiki, A., Nakamura, M., Arakawa, T., et al. (2003). Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage. Proc. Natl. Acad. Sci. USA. 100, 15776–15781. https://doi.org/10.1073/pnas.2136655100.

80. Schwalb, B., Michel, M., Zacher, B., Fru€hauf, K., Demel, C., Tresch, A., Gagneur, J., and Cramer, P. (2016). TT-seq maps the human transient transcriptome. Science 352, 1225–1228. https://doi.org/10.1126/sci- ence.aad9841.

81. Core, L.J., Martins, A.L., Danko, C.G., Waters, C.T., Siepel, A., and Lis, J.T. (2014). Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nat. Genet. 46, 1311–1320. https://doi.org/10.1038/ng.3142.

82. Shehata, M., Waterhouse, P.D., Casey, A.E., Fang, H., Hazelwood, L., and Khokha, R. (2018). Proliferative heterogeneity of murine epithelial cells in the adult mammary gland. Commun. Biol. 1, 111.

83. Stro¨ m, A., Hartman, J., Foster, J.S., Kietz, S., Wimalasena, J., and Gustafs- son, J.A. (2004). Estrogen receptor beta inhibits 17beta-estradiol-stimu- lated proliferation of the breast cancer cell line T47D. Proc. Natl. Acad. Sci. USA. 101, 1566–1571. https://doi.org/10.1073/pnas.0308319100.

84. Itou, J., Takahashi, R., Sasanuma, H., Tsuda, M., Morimoto, S., Matsu- moto, Y., Ishii, T., Sato, F., Takeda, S., and Toi, M. (2020). Estrogen in- duces mammary ductal dysplasia via the upregulation of myc expression in a dna-repair deficient condition. iScience, 100821.

85. Aymard, F., Bugler, B., Schmidt, C.K., Guillou, E., Caron, P., Briois, S., Iacovoni, J.S., Daburon, V., Miller, K.M., Jackson, S.P., and Legube, G. (2014). Transcriptionally active chromatin recruits homologous recombi- nation at DNA double-strand breaks. Nat. Struct. Mol. Biol. 21, 366–374. https://doi.org/10.1038/nsmb.2796.

86. Sherr, C.J., Beach, D., and Shapiro, G.I. (2016). Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov. 6, 353–367. https:// doi.org/10.1158/2159-8290.CD-15-0894.

87. Sun, Y., Saha, S., Wang, W., Saha, L.K., Huang, S.Y.N., and Pommier, Y. (2020). Excision repair of topoisomerase DNA-protein crosslinks (TOP- DPC). DNA Repair 89, 102837. https://doi.org/10.1016/j.dnarep.2020. 102837.

88. Wang, H., Shi, L.Z., Wong, C.C.L., Han, X., Hwang, P.Y.-H., Truong, L.N., Zhu, Q., Shao, Z., Chen, D.J., Berns, M.W., et al. (2013). The interaction of CtIP and Nbs1 connects CDK and ATM to regulate HR-mediated double- strand break repair. PLoS Genet. 9, e1003277. https://doi.org/10.1371/ journal.pgen.1003277.

89. Huertas, P., and Jackson, S.P. (2009). Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J. Biol. Chem. 284, 9558–9565. https://doi.org/10.1074/jbc.M808906200.

90. Yun, M.H., and Hiom, K. (2009). CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle. Na- ture 459, 460–463. https://doi.org/10.1038/nature07955.

91. Peterson, S.E., Li, Y., Wu-Baer, F., Chait, B.T., Baer, R., Yan, H., Gottes- man, M.E., and Gautier, J. (2013). Activation of DSB processing requires phosphorylation of CtIP by ATR. Mol. Cell 49, 657–667. https://doi.org/ 10.1016/j.molcel.2012.11.020.

92. Polato, F., Callen, E., Wong, N., Faryabi, R., Bunting, S., Chen, H.-T., Ko- zak, M., Kruhlak, M.J., Reczek, C.R., Lee, W.-H., et al. (2014). CtIP-medi- ated resection is essential for viability and can operate independently of BRCA1. J. Exp. Med. 211, 1027–1036. https://doi.org/10.1084/jem. 20131939.

93. Makharashvili, N., and Paull, T.T. (2015). CtIP: a DNA damage response protein at the intersection of DNA metabolism. DNA Repair 32, 75–81.

94. Aparicio, T., Baer, R., Gottesman, M., and Gautier, J. (2016). MRN, CtIP, and BRCA1 mediate repair of topoisomerase II-DNA adducts. J. Cell Biol. 212, 399–408. https://doi.org/10.1083/jcb.201504005.

95. Anand, R., Jasrotia, A., Bundschuh, D., Howard, S.M., Ranjha, L., Stucki, M., and Cejka, P. (2019). NBS1 promotes the endonuclease activity of the MRE11-RAD50 complex by sensing CtIP phosphorylation. EMBO J. 38, e101005. https://doi.org/10.15252/embj.2018101005.

96. Anand, R., Ranjha, L., Cannavo, E., and Cejka, P. (2016). Phosphorylated CtIP functions as a Co-factor of the MRE11-RAD50-NBS1 endonuclease in DNA end resection. Mol. Cell 64, 940–950. https://doi.org/10.1016/j. molcel.2016.10.017.

97. Deshpande, R.A., Myler, L.R., Soniat, M.M., Makharashvili, N., Lee, L., Lees-Miller, S.P., Finkelstein, I.J., and Paull, T.T. (2020). DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP. Sci. Adv. 6, eaay0922. https://doi.org/10.1126/sciadv.aay0922.

98. Nakamura, K., Kogame, T., Oshiumi, H., Shinohara, A., Sumitomo, Y., Agama, K., Pommier, Y., Tsutsui, K.M., Tsutsui, K., Hartsuiker, E., et al. (2010). Collaborative action of Brca1 and CtIP in elimination of covalent modifications from double-strand breaks to facilitate subsequent break repair. PLoS Genet. 6, e1000828. https://doi.org/10.1371/journal.pgen. 1000828.

99. Biehs, R., Steinlage, M., Barton, O., Juha´ sz, S., Ku€nzel, J., Spies, J., Shi- bata, A., Jeggo, P.A., and Lo¨ brich, M. (2017). DNA double-strand break resection occurs during non-homologous end joining in G1 but is distinct from resection during homologous recombination. Mol. Cell 65, 671– 684.e5. https://doi.org/10.1016/j.molcel.2016.12.016.

100. Barton, O., Naumann, S.C., Diemer-Biehs, R., Ku€nzel, J., Steinlage, M., Conrad, S., Makharashvili, N., Wang, J., Feng, L., Lopez, B.S., et al. (2014). Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1. J. Cell Biol. 206, 877–894. https://doi.org/10.1083/jcb. 201401146.

101. Ben-David, U., Siranosian, B., Ha, G., Tang, H., Oren, Y., Hinohara, K., Strathdee, C.A., Dempster, J., Lyons, N.J., Burns, R., et al. (2018). Ge- netic and transcriptional evolution alters cancer cell line drug response. Nature 560, 325–330. https://doi.org/10.1038/s41586-018-0409-3.

102. Meitinger, F., Ohta, M., Lee, K.Y., Watanabe, S., Davis, R.L., Anzola, J.V., Kabeche, R., Jenkins, D.A., Shiau, A.K., Desai, A., and Oegema, K. (2020). TRIM37 controls cancer-specific vulnerability to PLK4 inhibition. Nature 585, 440–446. https://doi.org/10.1038/s41586-020-2710-1.

103. Hurtado, A., Holmes, K.A., Ross-Innes, C.S., Schmidt, D., and Carroll, J.S. (2011). FOXA1 is a key determinant of estrogen receptor function and endocrine response. Nat. Genet. 43, 27–33. https://doi.org/10. 1038/ng.730.

104. Haberle, V., and Stark, A. (2018). Eukaryotic core promoters and the functional basis of transcription initiation. Nat. Rev. Mol. Cell Biol. 19, 621–637. https://doi.org/10.1038/s41580-018-0028-8.

105. Carninci, P., Sandelin, A., Lenhard, B., Katayama, S., Shimokawa, K., Ponjavic, J., Semple, C.A.M., Taylor, M.S., Engstro¨ m, P.G., Frith, M.C., et al. (2006). Genome-wide analysis of mammalian promoter architecture and evolution. Nat. Genet. 38, 626–635. https://doi.org/10.1038/ng1789.

106. Zabidi, M.A., and Stark, A. (2016). Regulatory enhancer-core-promoter communication via transcription factors and cofactors. Trends Genet. 32, 801–814. https://doi.org/10.1016/j.tig.2016.10.003.

107. Maqbool, M.A., Pioger, L., El Aabidine, A.Z., Karasu, N., Molitor, A.M., Dao, L.T.M., Charbonnier, G., van Laethem, F., Fenouil, R., Koch, F., et al. (2020). Alternative enhancer usage and targeted polycomb marking hallmark promoter choice during T cell differentiation. Cell Rep. 32, 108048. https://doi.org/10.1016/j.celrep.2020.108048.

108. Bardales, J.A., Wieser, E., Kawaji, H., Murakawa, Y., and Darzacq, X. (2018). Selective activation of alternative. Genes 9, 270. https://doi.org/ 10.3390/genes9060270.

109. Lopes, R., Sprouffske, K., Sheng, C., Uijttewaal, E.C.H., Wesdorp, A.E., Dahinden, J., Wengert, S., Diaz-Miyar, J., Yildiz, U., Bleu, M., et al. (2021). Systematic dissection of transcriptional regulatory networks by genome- scale and single-cell CRISPR screens. Sci. Adv. 7, eabf5733. https://doi. org/10.1126/sciadv.abf5733.

110. Shanbhag, N.M., Rafalska-Metcalf, I.U., Balane-Bolivar, C., Janicki, S.M., and Greenberg, R.A. (2010). ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 141, 970–981. https://doi.org/10.1016/j.cell.2010.04.038.

111. Caron, P., van der Linden, J., and van Attikum, H. (2019). Bon voyage: a transcriptional journey around DNA breaks. DNA Repair 82, 102686. https://doi.org/10.1016/j.dnarep.2019.102686.

112. Dekker, J., Rippe, K., Dekker, M., and Kleckner, N. (2002). Capturing chromosome conformation. Science 295, 1306–1311. https://doi.org/ 10.1126/science.1067799.

113. Davies, J.O.J., Oudelaar, A.M., Higgs, D.R., and Hughes, J.R. (2017). How best to identify chromosomal interactions: a comparison of approaches. Nat. Methods 14, 125–134. https://doi.org/10.1038/nmeth.4146.

114. Madabhushi, R., Gao, F., Pfenning, A.R., Pan, L., Yamakawa, S., Seo, J., Rueda, R., Phan, T.X., Yamakawa, H., Pao, P.C., et al. (2015). Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 161, 1592–1605. https://doi.org/10.1016/j.cell.2015.05.032.

115. Sun, P., Yuan, Y., Li, A., Li, B., and Dai, X. (2010). Cytokeratin expression during mouse embryonic and early postnatal mammary gland develop- ment. Histochem. Cell Biol. 133, 213–221. https://doi.org/10.1007/ s00418-009-0662-5.

116. Hart, J.R., Garner, A.L., Yu, J., Ito, Y., Sun, M., Ueno, L., Rhee, J.-K., Baksh, M.M., Stefan, E., Hartl, M., et al. (2014). Inhibitor of MYC identified in a Kro¨ hnke pyridine library. Proc. Natl. Acad. Sci. USA. 111, 12556– 12561.

117. Al Mahmud, M.R., Ishii, K., Bernal-Lozano, C., Delgado-Sainz, I., Toi, M., Akamatsu, S., Fukumoto, M., Watanabe, M., Takeda, S., Corte´ s-Ledesma, F., and Sasanuma, H. (2020). TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands. Gene Cell. 25, 450–465. https://doi.org/10.1111/ gtc.12770.

118. Sun, Y., Chen, J., Huang, S.Y.N., Su, Y.P., Wang, W., Agama, K., Saha, S., Jenkins, L.M., Pascal, J.M., and Pommier, Y. (2021). PARylation pre- vents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation. Nat. Commun. 12, 5010. https://doi.org/10.1038/s41467-021-25252-9.

119. Das, S.K., Kuzin, V., Cameron, D.P., Sanford, S., Jha, R.K., Nie, Z., Rose- llo, M.T., Holewinski, R., Andresson, T., Wisniewski, J., et al. (2022). MYC assembles and stimulates topoisomerases 1 and 2 in a "topoisome. Mol. Cell 82, 140–158.e12. https://doi.org/10.1016/j.molcel.2021.11.016.

120. Harding, S.M., Boiarsky, J.A., and Greenberg, R.A. (2015). ATM dependent silencing links nucleolar chromatin reorganization to DNA damage recogni- tion. Cell Rep. 13, 251–259. https://doi.org/10.1016/j.celrep.2015.08.085.

121. Purman, C.E., Collins, P.L., Porter, S.I., Saini, A., Gupta, H., Sleckman, B.P., and Oltz, E.M. (2019). Regional gene repression by DNA double- strand breaks in G. Mol. Cell Biol. 39, e00181–e00219. https://doi.org/ 10.1128/MCB.00181-19.

122. Meisenberg, C., Pinder, S.I., Hopkins, S.R., Wooller, S.K., Benstead- Hume, G., Pearl, F.M.G., Jeggo, P.A., and Downs, J.A. (2019). Repres- sion of transcription at DNA breaks requires cohesin throughout inter- phase and prevents genome instability. Mol. Cell 73, 212–223.e7. https://doi.org/10.1016/j.molcel.2018.11.001.

123. Larsen, D.H., Hari, F., Clapperton, J.A., Gwerder, M., Gutsche, K., Alt- meyer, M., Jungmichel, S., Toledo, L.I., Fink, D., Rask, M.B., et al. (2014). The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage. Nat. Cell Biol. 16, 792–803. https://doi.org/ 10.1038/ncb3007.

124. Marnef, A., and Legube, G. (2021). R-loops as Janus-faced modulators of DNA repair. Nat. Cell Biol. 23, 305–313. https://doi.org/10.1038/s41556- 021-00663-4.

125. Pedersen, B.S., and De, S. (2013). Loss of heterozygosity preferentially occurs in early replicating regions in cancer genomes. Nucleic Acids Res. 41, 7615–7624. https://doi.org/10.1093/nar/gkt552.

126. Mateo, J., Carreira, S., Sandhu, S., Miranda, S., Mossop, H., Perez-Lopez, R., Nava Rodrigues, D., Robinson, D., Omlin, A., Tunariu, N., et al. (2015). DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373, 1697–1708. https://doi.org/10.1056/NEJMoa1506859.

127. Pritchard, C.C., Mateo, J., Walsh, M.F., De Sarkar, N., Abida, W., Beltran, H., Garofalo, A., Gulati, R., Carreira, S., Eeles, R., et al. (2016). Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N. Engl. J. Med. 375, 443–453. https://doi.org/10.1056/NEJMoa1603144.

128. Van Keymeulen, A., Lee, M.Y., Ousset, M., Brohe´ e, S., Rorive, S., Gir- addi, R.R., Wuidart, A., Bouvencourt, G., Dubois, C., Salmon, I., et al. (2015). Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity. Nature 525, 119–123. https://doi.org/10. 1038/nature14665.

129. Koren, S., Reavie, L., Couto, J.P., De Silva, D., Stadler, M.B., Roloff, T., Britschgi, A., Eichlisberger, T., Kohler, H., Aina, O., et al. (2015). PIK3- CA(H1047R) induces multipotency and multi-lineage mammary tumours. Nature 525, 114–118. https://doi.org/10.1038/nature14669.

130. Lim, E., Vaillant, F., Wu, D., Forrest, N.C., Pal, B., Hart, A.H., Asselin- Labat, M.-L., Gyorki, D.E., Ward, T., Partanen, A., et al. (2009). Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat. Med. 15, 907–913. https://doi.org/10.1038/nm.2000.

131. Koren, S., and Bentires-Alj, M. (2015). Breast tumor heterogeneity: source of fitness, hurdle for therapy. Mol. Cell 60, 537–546. https://doi. org/10.1016/j.molcel.2015.10.031.

132. Wang, L., and Di, L.J. (2014). BRCA1 and estrogen/estrogen receptor in breast cancer: where they interact? Int. J. Biol. Sci. 10, 566–575. https:// doi.org/10.7150/ijbs.8579.

133. Shiloh, Y., and Ziv, Y. (2013). The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat. Rev. Mol. Cell Biol. 14, 197–210. https://doi.org/10.1038/nrm3546.

134. Savitsky, K., Barshira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Ta- gle, D.A., Smith, S., Uziel, T., Sfez, S., et al. (1995). A single ataxia-telan- giectasia gene with a product similar to PI-3 kinase. Science 268, 1749– 1753. https://doi.org/10.1126/science.7792600.

135. Hoa, N.N., Akagawa, R., Yamasaki, T., Hirota, K., Sasa, K., Natsume, T., Kobayashi, J., Sakuma, T., Yamamoto, T., Komatsu, K., et al. (2015). Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines. Gene Cell. 20, 1059–1076. https://doi.org/10.1111/gtc.12310.

136. Herzog, K.H., Chong, M.J., Kapsetaki, M., Morgan, J.I., and McKinnon, P.J. (1998). Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system. Science 280, 1089–1091. https://doi.org/10.1126/science.280.5366.1089.

137. Barlow, C., Hirotsune, S., Paylor, R., Liyanage, M., Eckhaus, M., Collins, F., Shiloh, Y., Crawley, J.N., Ried, T., Tagle, D., and WynshawBoris, A. (1996). Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell 86, 159–171. https://doi.org/10.1016/s0092-8674(00)80086-0.

138. Kim, D., Langmead, B., and Salzberg, S.L. (2015). HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12, 357–360. https://doi.org/10.1038/nmeth.3317.

139. Haberle, V., Forrest, A.R.R., Hayashizaki, Y., Carninci, P., and Lenhard, B. (2015). CAGEr: precise TSS data retrieval and high-resolution promo- terome mining for integrative analyses. Nucleic Acids Res. 43, e51. https://doi.org/10.1093/nar/gkv054.

140. Frith, M.C., Valen, E., Krogh, A., Hayashizaki, Y., Carninci, P., and Sande- lin, A. (2008). A code for transcription initiation in mammalian genomes. Genome Res. 18, 1–12. https://doi.org/10.1101/gr.6831208.

141. Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550. https://doi.org/10.1186/s13059-014-0550-8.

142. Frietze, S., Wang, R., Yao, L., Tak, Y.G., Ye, Z., Gaddis, M., Witt, H., Farn- ham, P.J., and Jin, V.X. (2012). Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3. Genome Biol. 13, R52. https://doi.org/10.1186/gb-2012-13-9-r52.

143. Liu, T., Ortiz, J.A., Taing, L., Meyer, C.A., Lee, B., Zhang, Y., Shin, H., Wong, S.S., Ma, J., Lei, Y., et al. (2011). Cistrome: an integrative platform for transcriptional regulation studies. Genome Biol. 12, R83. https://doi. org/10.1186/gb-2011-12-8-r83.

144. Zhang, Y., Zhang, D., Li, Q., Liang, J., Sun, L., Yi, X., Chen, Z., Yan, R., Xie, G., Li, W., et al. (2016). Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering. Nat. Genet. 48, 1003–1013. https://doi.org/10.1038/ng.3635.

145. Mohammed, H., Russell, I.A., Stark, R., Rueda, O.M., Hickey, T.E., Tarulli, G.A., Serandour, A.A., Birrell, S.N., Bruna, A., Saadi, A., et al. (2015). Pro- gesterone receptor modulates ERa action in breast cancer. Nature 523, 313–317. https://doi.org/10.1038/nature14583.

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