The 9-1-1 Complex Controls Mre11 Nuclease and Checkpoint Activation during Short-Range Resection of DNA Double-Strand Breaks

Autor: Elisa Gobbini, Erika Casari, Chiara Vittoria Colombo, Diego Bonetti, Maria Pia Longhese
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports, Vol 33, Iss 3, Pp 108287- (2020)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.108287
Popis: Summary: Homologous recombination is initiated by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection is a two-step process in which an initial short-range step is catalyzed by the Mre11-Rad50-Xrs2 (MRX) complex and limited to the vicinity of the DSB end. Then the two long-range resection Exo1 and Dna2-Sgs1 nucleases extend the resected DNA tracts. How short-range resection is regulated and contributes to checkpoint activation remains to be determined. Here, we show that abrogation of long-range resection induces a checkpoint response that decreases DNA damage resistance. This checkpoint depends on the 9-1-1 complex, which recruits Dpb11 and Rad9 at damaged DNA. Furthermore, the 9-1-1 complex, independently of Dpb11 and Rad9, restricts short-range resection by negatively regulating Mre11 nuclease. We propose that 9-1-1, which is loaded at the leading edge of resection, plays a key function in regulating Mre11 nuclease and checkpoint activation once DSB resection is initiated.
Databáze: Directory of Open Access Journals