The role of ATF7 in the maintenance of stress-induced telomere shortening

概要

1. Telomere and Telomerase
1.1. Telomere and Telomere length
Telomeres were identified in the 1930s. It is typical heterochromatin region which
located at the ends of chromosomes, composed of tandem repeats that are bound with
shelterin multi-protein complex. The telomere structures are critical for chromosome
integrity.
Telomeric DNA has typically heterochromatin structure composed of multiple
short repeats that are often G/T rich. The mammalian telomeres are composed of
double-stranded TTAGGG repeats and a single-stranded telomeric 3’ tail end. The
telomere lengths are variable among different species, for example telomere extends
for 9-15 kb in humans but 100 kb in rodents. The telomere structure is characterized
of T-loop and D-loop that is due to fold back and invade of telomere 3’-overhang to
the double stranded region (Fig. 1-1A) [1].
Shelterin protein complex is known to cap with telomeric DNA. In mammals,
there are six proteins: telomeric repeat-binding factor 1 (TRF1), TRF2, repressor and
activator protein 1 (RAP1), TRF1-interacting nuclear protein 2 (TIN2), protection of
telomeres 1 (POT1) and TPP1 (Fig.1-1A). In S. cerevisiae, Rap1, Cdc13, Stn1 and
Ten1, chromosome end-binding proteins, are cap with telomere. In addition, Taz1
(homolog of TRF), Rap1, Pot1, Tpz1, Poz1 and Ccq1 (coiled-coil quantitativelyenriched 1) were reported to bind on the telomere forming the shelterin complex in
yeast S. pombe [2]. Furthermore, some other proteins such as Ku70/80, yeast sir4,
bind to telomere region. Ku70 and Ku80 are conserved from mammal to yeast, which
are well known to form a heterodimer and contribute to DNA repair. The Ku
heterodimer binds to double-stranded DNA (dsDNA) in a structure-specific and
sequence-independent manner, and mediate a non-homologous end joining (NHEJ) to
repair the DNA double-strand breaks. On telomere, the Ku heterodimer has a specific
high-affinity interaction with TRF1 complex, acting in a unique way to prevent
chromatin recombination. In addition, Ku complex could regulate the telomere length.
Ku-mediated telomerase recruitment was reported in yeast and human [3-6]. ...

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