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.

Basic information

Original name

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

Authors

KOLINJIVADI, A.M. (380 Italy), V. SANNINO (380 Italy), A. DE ANTONI (380 Italy), Karina MOVSESJAN (417 Kyrgyzstan, belonging to the institution), M. KILKENNY (826 United Kingdom of Great Britain and Northern Ireland), H. TECHER (380 Italy), G. BALDI (380 Italy), R. SHEN (826 United Kingdom of Great Britain and Northern Ireland), A. CICCIA (840 United States of America), L. PELLEGRINI (826 United Kingdom of Great Britain and Northern Ireland), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution) and V. COSTANZO (380 Italy)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 14.248

RIV identification code

RIV/00216224:14110/17:00095171

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.molcel.2017.07.001

UT WoS

000411128900014

Keywords in English

Brca2

Abstract

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.

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

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 and 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, vol. 67, No 5, p. "867"-"+", 22 pp. ISSN 1097-2765. Available from: https://dx.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 = {http://dx.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 and 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, vol.~67, No~5, p.~''867''-''+'', 22 pp. ISSN~1097-2765. Available from: https://dx.doi.org/10.1016/j.molcel.2017.07.001.

Detailed Information on Publication Record