RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Molecular Cell |
Volume | 66 |
Issue number | 5 |
Pages (from-to) | 658-671.e8 |
ISSN | 1097-2765 |
DOIs | |
Publication status | Published - 1 Jun 2017 |
- Binding Sites, Chromosomal Instability, Chromosome Fragile Sites, Chromosome Segregation, Cyclin-Dependent Kinases, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Endodeoxyribonucleases, Endonucleases, HEK293 Cells, HeLa Cells, Humans, Mitosis, Phosphorylation, Protein Binding, RNA Interference, Rad51 Recombinase, RecQ Helicases, Replication Origin, Time Factors, Transfection, Journal Article
Research areas
ID: 185901602