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.
Galli, M., Frigerio, C., Longhese, M., & Clerici, M. (2021). The regulation of the DNA damage response at telomeres: Focus on kinases. BIOCHEMICAL SOCIETY TRANSACTIONS, 49(2), 933-943 [10.1042/BST20200856].
|Citazione:||Galli, M., Frigerio, C., Longhese, M., & Clerici, M. (2021). The regulation of the DNA damage response at telomeres: Focus on kinases. BIOCHEMICAL SOCIETY TRANSACTIONS, 49(2), 933-943 [10.1042/BST20200856].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||The regulation of the DNA damage response at telomeres: Focus on kinases|
|Autori:||Galli, M; Frigerio, C; Longhese, M; Clerici, M|
GALLI, MICHELA (Primo) [Membro del Collaboration Group]
CLERICI, MICHELA (Ultimo) [Membro del Collaboration Group] (Corresponding)
|Data di pubblicazione:||2021|
|Rivista:||BIOCHEMICAL SOCIETY TRANSACTIONS|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1042/BST20200856|
|Appare nelle tipologie:||01 - Articolo su rivista|