RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články
PubMed
28575661
DOI
10.1016/j.molcel.2017.05.006
PII: S1097-2765(17)30319-2
Knihovny.cz E-zdroje
- Klíčová slova
- MUS81, RAD51 filament, RECQ5, common fragile sites, genomic instability, mitotic DNA synthesis, replication stress,
- MeSH
- časové faktory MeSH
- chromozomální nestabilita MeSH
- cyklin-dependentní kinasy metabolismus MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- DNA biosyntéza genetika MeSH
- endodeoxyribonukleasy metabolismus MeSH
- endonukleasy genetika metabolismus MeSH
- fosforylace MeSH
- fragilní místa na chromozomu * MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- helikasy RecQ genetika metabolismus MeSH
- lidé MeSH
- mitóza * MeSH
- oprava DNA * MeSH
- poškození DNA MeSH
- proteinkinasa CDC2 MeSH
- rekombinasa Rad51 metabolismus MeSH
- replikační počátek * MeSH
- RNA interference MeSH
- segregace chromozomů MeSH
- transfekce MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CDK1 protein, human MeSH Prohlížeč
- cyklin-dependentní kinasy MeSH
- DNA vazebné proteiny MeSH
- DNA MeSH
- Eme1 protein, human MeSH Prohlížeč
- endodeoxyribonukleasy MeSH
- endonukleasy MeSH
- helikasy RecQ MeSH
- MUS81 protein, human MeSH Prohlížeč
- proteinkinasa CDC2 MeSH
- RAD51 protein, human MeSH Prohlížeč
- RECQL5 protein, human MeSH Prohlížeč
- rekombinasa Rad51 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
Citace poskytuje 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
