RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis
Language English Country United States Media print
Document type Journal Article
PubMed
28575661
DOI
10.1016/j.molcel.2017.05.006
PII: S1097-2765(17)30319-2
Knihovny.cz E-resources
- Keywords
- MUS81, RAD51 filament, RECQ5, common fragile sites, genomic instability, mitotic DNA synthesis, replication stress,
- MeSH
- Time Factors MeSH
- Chromosomal Instability MeSH
- Cyclin-Dependent Kinases metabolism MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- DNA biosynthesis genetics MeSH
- Endodeoxyribonucleases metabolism MeSH
- Endonucleases genetics metabolism MeSH
- Phosphorylation MeSH
- Chromosome Fragile Sites * MeSH
- HEK293 Cells MeSH
- HeLa Cells MeSH
- RecQ Helicases genetics metabolism MeSH
- Humans MeSH
- Mitosis * MeSH
- DNA Repair * MeSH
- DNA Damage MeSH
- CDC2 Protein Kinase MeSH
- Rad51 Recombinase metabolism MeSH
- Replication Origin * MeSH
- RNA Interference MeSH
- Chromosome Segregation MeSH
- Transfection MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- CDK1 protein, human MeSH Browser
- Cyclin-Dependent Kinases MeSH
- DNA-Binding Proteins MeSH
- DNA MeSH
- Eme1 protein, human MeSH Browser
- Endodeoxyribonucleases MeSH
- Endonucleases MeSH
- RecQ Helicases MeSH
- MUS81 protein, human MeSH Browser
- CDC2 Protein Kinase MeSH
- RAD51 protein, human MeSH Browser
- RECQL5 protein, human MeSH Browser
- Rad51 Recombinase MeSH
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.
Department of Biology Faculty of Medicine Masaryk University Kamenice 5 A7 Brno 62500 Czech Republic
References provided by Crossref.org
Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors
MUS81 cleaves TOP1-derived lesions and other DNA-protein cross-links
RECQ5: A Mysterious Helicase at the Interface of DNA Replication and Transcription
