RT Journal Article
SR Electronic
T1 Persistent telomere cohesion protects aged cells from premature senescence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.03.932145
DO 10.1101/2020.02.03.932145
A1 Azarm, Kameron
A1 Bhardwaj, Amit
A1 Kim, Eugenie
A1 Smith, Susan
YR 2020
UL http://biorxiv.org/content/early/2020/02/03/2020.02.03.932145.abstract
AB Human telomeres are bound by the telomere repeat binding proteins TRF1 and TRF2. Telomere shortening in human cells leads to a DNA damage response that signals replicative senescence. While insufficient loading of TRF2 at shortened telomeres contributes to the DNA damage response in senescence, the contribution of TRF1 to senescence induction has not been determined. Here we show that counter to TRF2 deficiency-mediated induction of DNA damage, TRF1 deficiency serves a protective role to limit induction of DNA damage induced by subtelomere recombination. Shortened telomeres recruit insufficient TRF1 and as a consequence inadequate tankyrase 1 to resolve sister telomere cohesion. The persistent cohesion protects short telomeres from inappropriate recombination. Ultimately, in the final division, telomeres are no longer able to maintain cohesion and subtelomere copying ensues. Thus, the gradual loss of TRF1 and concomitant persistent cohesion that occurs with telomere shortening ensures a measured approach to replicative senescence.