RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing
Stalled Replication Forks at Common Fragile Sites during
Mitosis

J 2017

RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis

DI MARCO, Stefano; Zdenka HAŠANOVÁ; Radhakrishnan KANAGARAJ; Nagaraja CHAPPIDI; Veronika ALTMANNOVÁ et. al.

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

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

https://doi.org/10.1016/j.molcel.2017.05.006

UT WoS

000402726700009

EID Scopus

2-s2.0-85020070786

Keywords in English

common fragile sites; genomic instability; mitotic DNA synthesis; MUS81; RAD51 filament; RECQ5; replication stress

Abstract

In the original language

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 project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

GA17-17720S, research and development project

Name: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Czech Science Foundation

MUNI/M/1894/2014, interní kód MU

Name: Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

Cite

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://doi.org/10.1016/j.molcel.2017.05.006.

@article{1389297,
   author = {Di Marco, Stefano and Hašanová, Zdenka and Kanagaraj, Radhakrishnan and Chappidi, Nagaraja and Altmannová, Veronika and Menon, Shruti and Sedláčková, Hana and Langhoff, Jana and Surendranath, Kalpana and Hühn, Daniela and Bhowmick, Rahul and Marini Palomeque, María Victoria and Ferrari, Stefano and Hickson, Ian D. and Krejčí, Lumír and Janscak, Pavel},
   article_location = {CAMBRIDGE},
   article_number = {5},
   doi = {https://doi.org/10.1016/j.molcel.2017.05.006},
   keywords = {common fragile sites; genomic instability; mitotic DNA synthesis; MUS81; RAD51 filament; RECQ5; replication stress},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis},
   volume = {66},
   year = {2017}
}

TY  - JOUR
ID  - 1389297
AU  - Di Marco, Stefano - Hašanová, Zdenka - Kanagaraj, Radhakrishnan - Chappidi, Nagaraja - Altmannová, Veronika - Menon, Shruti - Sedláčková, Hana - Langhoff, Jana - Surendranath, Kalpana - Hühn, Daniela - Bhowmick, Rahul - Marini Palomeque, María Victoria - Ferrari, Stefano - Hickson, Ian D. - Krejčí, Lumír - Janscak, Pavel
PY  - 2017
TI  - RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis
JF  - Molecular Cell
VL  - 66
IS  - 5
SP  - "658"-"+"
EP  - "658"-"+"
PB  - CELL PRESS
SN  - 10972765
KW  - common fragile sites
KW  - genomic instability
KW  - mitotic DNA synthesis
KW  - MUS81
KW  - RAD51 filament
KW  - RECQ5
KW  - replication stress
N2  - 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.
ER  -

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. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2017, vol.~66, No~5, p.~''658''-''+'', 22 pp. ISSN~1097-2765. Available from: https://doi.org/10.1016/j.molcel.2017.05.006.

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