DI MARCO, Stefano, Zdenka HAŠANOVÁ, Radhakrishnan KANAGARAJ, Nagaraja CHAPPIDI, Veronika ALTMANNOVÁ, Shruti MENON, Hana SEDLÁČKOVÁ, Jana LANGHOFF, Kalpana SURENDRANATH, Daniela HÜHN, Rahul BHOWMICK, María Victoria MARINI PALOMEQUE, Stefano FERRARI, Ian D. HICKSON, Lumír KREJČÍ and Pavel JANSCAK. RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Molecular Cell. CAMBRIDGE: CELL PRESS, 2017, vol. 66, No 5, p. "658"-"+", 22 pp. ISSN 1097-2765. Available from: https://dx.doi.org/10.1016/j.molcel.2017.05.006.
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Basic information
Original name RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis
Authors DI MARCO, Stefano (756 Switzerland), Zdenka HAŠANOVÁ (703 Slovakia, belonging to the institution), Radhakrishnan KANAGARAJ (756 Switzerland), Nagaraja CHAPPIDI (756 Switzerland), Veronika ALTMANNOVÁ (203 Czech Republic, belonging to the institution), Shruti MENON (756 Switzerland), Hana SEDLÁČKOVÁ (203 Czech Republic, belonging to the institution), Jana LANGHOFF (756 Switzerland), Kalpana SURENDRANATH (826 United Kingdom of Great Britain and Northern Ireland), Daniela HÜHN (756 Switzerland), Rahul BHOWMICK (208 Denmark), María Victoria MARINI PALOMEQUE (858 Uruguay, belonging to the institution), Stefano FERRARI (756 Switzerland), Ian D. HICKSON (208 Denmark), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution) and Pavel JANSCAK (756 Switzerland).
Edition Molecular Cell, CAMBRIDGE, CELL PRESS, 2017, 1097-2765.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 14.248
RIV identification code RIV/00216224:14110/17:00094931
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1016/j.molcel.2017.05.006
UT WoS 000402726700009
Keywords in English common fragile sites; genomic instability; mitotic DNA synthesis; MUS81; RAD51 filament; RECQ5; replication stress
Tags EL OK, podil
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 8/3/2018 12:41.
Abstract
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 30-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.
Links
GA13-26629S, research and development projectName: SUMO a stability genomu
Investor: Czech Science Foundation
GA17-17720S, research and development projectName: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace
Investor: Czech Science Foundation
MUNI/M/1894/2014, interní kód MUName: Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
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