The natural ends of linear chromosomes resemble those of accidental double-strand breaks (DSBs). DSBs induce a multifaceted cellular response that promotes the repair of lesions and slows down cell cycle progression. This response is not elicited at chromosome ends, which are organized in nucleoprotein structures called telomeres. Besides counteracting DSB response through specialized telomere-binding proteins, telomeres also prevent chromosome shortening. Despite of the different fate of telomeres and DSBs, many proteins involved in the DSB response also localize at telomeres and participate in telomere homeostasis. In particular, the DSB master regulators Tel1/ATM and Mec1/ATR contribute to telomere length maintenance and arrest cell cycle progression when chromosome ends shorten, thus promoting a tumor-suppressive process known as replicative senescence. During senescence, the actions of both these apical kinases and telomere-binding proteins allow checkpoint activation while bulk DNA repair activities at telomeres are still inhibited. Checkpoint-mediated cell cycle arrest also prevents further telomere erosion and deprotection that would favor chromosome rearrangements, which are known to increase cancer-associated genome instability. This review summarizes recent insights into functions and regulation of Tel1/ATM and Mec1/ATR at telomeres both in the presence and in the absence of telomerase, focusing mainly on discoveries in budding yeast.
-
Cover Image
Cover Image
The cover image is an illustrative representation of chloroplast ATP synthases in a thylakoid membrane. In photosynthetic organisms the rotor complex of the ATP synthase (blue and cyan) is specifically adapted to physiological needs of the plant or cyanobacterial cell. For more details, see the review by Cheuk and Meier (pages 541–550). The figure was made by Anthony Cheuk.
The regulation of the DNA damage response at telomeres: focus on kinases Available to Purchase
Michela Galli, Chiara Frigerio, Maria Pia Longhese, Michela Clerici; The regulation of the DNA damage response at telomeres: focus on kinases. Biochem Soc Trans 30 April 2021; 49 (2): 933–943. doi: https://doi.org/10.1042/BST20200856
Download citation file:
Sign in
Sign in to your personal account
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Get Email Alerts
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |