Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent
Degradation of Nascent DNA in the Absence of Brca2 and Stable
Rad51 Nucleofilaments

J 2017

Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments

KOLINJIVADI, A.M.; V. SANNINO; A. DE ANTONI; Karina MOVSESJAN; M. KILKENNY et. al.

Základní údaje

Originální název

Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments

Autoři

KOLINJIVADI, A.M.; V. SANNINO; A. DE ANTONI; Karina MOVSESJAN; M. KILKENNY; H. TECHER; G. BALDI; R. SHEN; A. CICCIA; L. PELLEGRINI; Lumír KREJČÍ a V. COSTANZO

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/00216224:14110/17:00095171

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1016/j.molcel.2017.07.001

UT WoS

000411128900014

EID Scopus

2-s2.0-85026222599

Klíčová slova anglicky

Brca2

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 4. 2018 11:48, Soňa Böhmová

Anotace

V originále

Brca2 deficiency causes Mre11-dependent degradation of nascent DNA at stalled forks, leading to cell lethality. To understand the molecular mechanisms underlying this process, we isolated Xenopus laevis Brca2. We demonstrated that Brca2 protein prevents single-stranded DNA gap accumulation at replication fork junctions and behind them by promoting Rad51 binding to replicating DNA. Without Brca2, forks with persistent gaps are converted by Smarcal1 into reversed forks, triggering extensive Mre11-dependent nascent DNA degradation. Stable Rad51 nucleofilaments, but not RPA or Rad51(T131P) mutant proteins, directly prevent Mre11-dependent DNA degradation. Mre11 inhibition instead promotes reversed fork accumulation in the absence of Brca2. Rad51 directly interacts with the Pol alpha N-terminal domain, promoting Pol alpha and delta binding to stalled replication forks. This interaction likely promotes replication fork restart and gap avoidance. These results indicate that Brca2 and Rad51 prevent formation of abnormal DNA replication intermediates, whose processing by Smarcal1 and Mre11 predisposes to genome instability.

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

Citovat

KOLINJIVADI, A.M.; V. SANNINO; A. DE ANTONI; Karina MOVSESJAN; M. KILKENNY; H. TECHER; G. BALDI; R. SHEN; A. CICCIA; L. PELLEGRINI; Lumír KREJČÍ a V. COSTANZO. Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments. Molecular Cell. CAMBRIDGE: CELL PRESS, 2017, roč. 67, č. 5, s. "867"-"+", 22 s. ISSN 1097-2765. Dostupné z: https://doi.org/10.1016/j.molcel.2017.07.001.

@article{1395556,
   author = {Kolinjivadi, A.M. and Sannino, V. and De Antoni, A. and Movsesjan, Karina and Kilkenny, M. and Techer, H. and Baldi, G. and Shen, R. and Ciccia, A. and Pellegrini, L. and Krejčí, Lumír and Costanzo, V.},
   article_location = {CAMBRIDGE},
   article_number = {5},
   doi = {https://doi.org/10.1016/j.molcel.2017.07.001},
   keywords = {Brca2},
   language = {eng},
   issn = {1097-2765},
   journal = {Molecular Cell},
   title = {Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments},
   volume = {67},
   year = {2017}
}

TY  - JOUR
ID  - 1395556
AU  - Kolinjivadi, A.M. - Sannino, V. - De Antoni, A. - Movsesjan, Karina - Kilkenny, M. - Techer, H. - Baldi, G. - Shen, R. - Ciccia, A. - Pellegrini, L. - Krejčí, Lumír - Costanzo, V.
PY  - 2017
TI  - Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments
JF  - Molecular Cell
VL  - 67
IS  - 5
SP  - "867"-"+"
EP  - "867"-"+"
PB  - CELL PRESS
SN  - 10972765
KW  - Brca2
N2  - Brca2 deficiency causes Mre11-dependent degradation of nascent DNA at stalled forks, leading to cell lethality. To understand the molecular mechanisms underlying this process, we isolated Xenopus laevis Brca2. We demonstrated that Brca2 protein prevents single-stranded DNA gap accumulation at replication fork junctions and behind them by promoting Rad51 binding to replicating DNA. Without Brca2, forks with persistent gaps are converted by Smarcal1 into reversed forks, triggering extensive Mre11-dependent nascent DNA degradation. Stable Rad51 nucleofilaments, but not RPA or Rad51(T131P) mutant proteins, directly prevent Mre11-dependent DNA degradation. Mre11 inhibition instead promotes reversed fork accumulation in the absence of Brca2. Rad51 directly interacts with the Pol alpha N-terminal domain, promoting Pol alpha and delta binding to stalled replication forks. This interaction likely promotes replication fork restart and gap avoidance. These results indicate that Brca2 and Rad51 prevent formation of abnormal DNA replication intermediates, whose processing by Smarcal1 and Mre11 predisposes to genome instability.
ER  -

KOLINJIVADI, A.M.; V. SANNINO; A. DE ANTONI; Karina MOVSESJAN; M. KILKENNY; H. TECHER; G. BALDI; R. SHEN; A. CICCIA; L. PELLEGRINI; Lumír KREJČÍ a V. COSTANZO. Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments. \textit{Molecular Cell}. CAMBRIDGE: CELL PRESS, 2017, roč.~67, č.~5, s.~''867''-''+'', 22 s. ISSN~1097-2765. Dostupné z: https://doi.org/10.1016/j.molcel.2017.07.001.

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