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.

Základní údaje

Originální název

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

Autoři

DI MARCO, Stefano (756 Švýcarsko), Zdenka HAŠANOVÁ (703 Slovensko, domácí), Radhakrishnan KANAGARAJ (756 Švýcarsko), Nagaraja CHAPPIDI (756 Švýcarsko), Veronika ALTMANNOVÁ (203 Česká republika, domácí), Shruti MENON (756 Švýcarsko), Hana SEDLÁČKOVÁ (203 Česká republika, domácí), Jana LANGHOFF (756 Švýcarsko), Kalpana SURENDRANATH (826 Velká Británie a Severní Irsko), Daniela HÜHN (756 Švýcarsko), Rahul BHOWMICK (208 Dánsko), María Victoria MARINI PALOMEQUE (858 Uruguay, domácí), Stefano FERRARI (756 Švýcarsko), Ian D. HICKSON (208 Dánsko), Lumír KREJČÍ (203 Česká republika, garant, domácí) a Pavel JANSCAK (756 Švýcarsko)

Vydání

Molecular Cell, CAMBRIDGE, CELL PRESS, 2017, 1097-2765

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 14.248

Kód RIV

RIV/00216224:14110/17:00094931

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000402726700009

Klíčová slova anglicky

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

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 3. 2018 12:41, Soňa Böhmová

Anotace

V originále

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.

Návaznosti

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

GA17-17720S, projekt VaV

Název: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Grantová agentura ČR, Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

MUNI/M/1894/2014, interní kód MU

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

Investor: Masarykova univerzita, Development of new MUS81 nuclease inhibitors as chemical biology probe with clinical progression, INTERDISCIPLINARY - Mezioborové výzkumné projekty

Citovat

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 a 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, roč. 66, č. 5, s. "658"-"+", 22 s. ISSN 1097-2765. Dostupné z: https://dx.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 = {http://dx.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 a 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, roč.~66, č.~5, s.~''658''-''+'', 22 s. ISSN~1097-2765. Dostupné z: https://dx.doi.org/10.1016/j.molcel.2017.05.006.

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