The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent on its Ser727 phosphorylation by CDK1. Upon replication stress, RECQ5 associates with CFSs in early mitosis through its physical interaction with MUS81 and promotes MUS81-dependent mitotic DNA synthesis. RECQ5 depletion or mutational inactivation of its ATP-binding site, RAD51-interacting domain, or phosphorylation site causes excessive binding of RAD51 to CFS loci and impairs CFS expression. This leads to defective chromosome segregation and accumulation of CFS-associated DNA damage in G1 cells. Biochemically, RECQ5 alleviates the inhibitory effect of RAD51 on 3'-flap DNA cleavage by MUS81-EME1 through its RAD51 filament disruption activity. These data suggest that RECQ5 removes RAD51 filaments stabilizing stalled replication forks at CFSs and hence facilitates CFS cleavage by MUS81-EME1.

Back to Main Page1. Please note that only one statement of equally contributing authors is allowed (as well as one statement of joint supervision, if appropriate), so the two present statements have been amalgamated into one for now. If the two pairs of authors need to be diffentiated, a statement can be added to the author contributions section to explain. If you would like to do this, please provide some text to add.The meer fact that two different statements were made was because they were not the same. So they must not be amalgamated.I have added a line in the Author Contribution section.2. First para of main text, sentence beginning "In yeast", please check that "SlX4" is correct. Should it be SLX4?It should be Slx4 with lowercase L and lowercase X 3. Please check your article carefully, coordinate with any co-authors and enter all final edits clearly in the eproof, remembering to save frequently. Once corrections are submitted, we cannot routinely make further changes to the article. OK 4. Note that the eproof should be amended in only one browser window at any one time; otherwise changes will be overwritten.OK 5. Author surnames have been highlighted. Please check these carefully and adjust if the first name or surname is marked up incorrectly. Note that changes here will affect indexing of your article in public repositories such as PubMed. Also, carefully check the spelling and numbering of all author names and affiliations, and the corresponding email address(es). OK 6. You cannot alter accepted Supplementary Information files except for critical changes to scientific content. If you do resupply any files, please also provide a brief (but complete) list of changes. If these are not considered scientific changes, any altered Supplementary files will not be used, only the originally accepted version will be published. OK 7. Para beginning "Here, we unravel" -please check that PCNA has been expanded correctly at first mention. e.Proofing https://eproofing.springer.com/journals_v2/printpage.php?token... 1 of 64 22/04/2020, 15:41 OK 8. Results section, first para, please define YFP at first mention Yellow fluorescent protein (YFP) Figure 1b -please define IgCThis is a typo. It should be IgG in the figure and the following definition added to the legend:IgG: Immunoglobulin G 10. Figure 1c, bottom axes of plots -please check that the jump from 10 h to 12 h is correct (the other time points are in increments of 1 h). Please also check that the labels added to the right of the immunoblots in panel c are correct.All is correct Figure 1 caption -please define HA at first mentionHemagglutinin (HA) Figure 1 -Please check carefully that the caption for panel c is correct as edited to match the new figure.All is OK In the caption to Figure 2g,h -please differentiate (by inserting (g) and (h) what the two panels show.The caption is the same for g and h. The only difference is that the mutations in g are missense mutations while they are nonsense mutations in h. I have changed the caption to:Co-immunoprecipitation of en...