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, vol. 67, No 5, p. "867"-"+", 22 pp. ISSN 1097-2765. doi:10.1016/j.molcel.2017.07.001. 2017.
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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
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/00216224:14110/17:00095171
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1016/j.molcel.2017.07.001
UT WoS 000411128900014
Keywords in English Brca2
Tags EL OK, podil
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 18/4/2018 11:48.
Abstract
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 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
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