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The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress
Author(s) -
TittelElmer Mireille,
Alabert Constance,
Pasero Philippe,
Cobb Jennifer A
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.60
Subject(s) - replisome , dna replication , biology , microbiology and biotechnology , genetics , g2 m dna damage checkpoint , genome instability , dna damage , cell cycle checkpoint , dna , eukaryotic dna replication , cell cycle , cell
The Mre11–Rad50–Xrs2 (MRX) complex has an important function in the maintenance of genomic integrity by contributing to the detection and repair of chromosome breaks. Here we show that the complex is recruited to sites of paused forks where it stabilizes the association of essential replisome components. Interestingly, this function is not dependent on the S phase checkpoint or the nuclease activity of Mre11. We find that disruption of the MRX complex leads to a loss of fork recovery and a failure to properly complete DNA replication when cells are exposed to replication stress. Our data suggest that one critical function of the MRX complex during replication is to promote the cohesion of sister chromatids at paused forks, offering an explanation for why MRX deficiency leads to a loss of cell viability and high levels of chromosome rearrangements under conditions of replication stress.