In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2022-11-14), p. e1010495-
Abstract:
Homologous recombination (HR) plays an essential role in the maintenance of genome stability by promoting the repair of cytotoxic DNA double strand breaks (DSBs). More recently, the HR pathway has emerged as a core component of the response to replication stress, in part by protecting stalled replication forks from nucleolytic degradation. In that regard, the mammalian RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) have been involved in both HR-mediated DNA repair and collapsed replication fork resolution. Still, it remains largely obscure how they participate in both processes, thereby maintaining genome stability and preventing cancer development. To gain better insight into their contribution in cellulo , we mapped the proximal interactome of the classical RAD51 paralogs using the BioID approach. Aside from identifying the well-established BCDX2 and CX3 sub-complexes, the spliceosome machinery emerged as an integral component of our proximal mapping, suggesting a crosstalk between this pathway and the RAD51 paralogs. Furthermore, we noticed that factors involved RNA metabolic pathways are significantly modulated within the BioID of the classical RAD51 paralogs upon exposure to hydroxyurea (HU), pointing towards a direct contribution of RNA processing during replication stress. Importantly, several members of these pathways have prognostic potential in breast cancer (BC), where their RNA expression correlates with poorer patient outcome. Collectively, this study uncovers novel functionally relevant partners of the different RAD51 paralogs in the maintenance of genome stability that could be used as biomarkers for the prognosis of BC.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010495
DOI:
10.1371/journal.pgen.1010495.g001
DOI:
10.1371/journal.pgen.1010495.g002
DOI:
10.1371/journal.pgen.1010495.g003
DOI:
10.1371/journal.pgen.1010495.g004
DOI:
10.1371/journal.pgen.1010495.g005
DOI:
10.1371/journal.pgen.1010495.s001
DOI:
10.1371/journal.pgen.1010495.s002
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10.1371/journal.pgen.1010495.s003
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10.1371/journal.pgen.1010495.s004
DOI:
10.1371/journal.pgen.1010495.s005
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10.1371/journal.pgen.1010495.s006
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10.1371/journal.pgen.1010495.s007
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10.1371/journal.pgen.1010495.s008
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10.1371/journal.pgen.1010495.s009
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10.1371/journal.pgen.1010495.s010
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10.1371/journal.pgen.1010495.s011
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10.1371/journal.pgen.1010495.s012
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10.1371/journal.pgen.1010495.s013
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10.1371/journal.pgen.1010495.s014
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10.1371/journal.pgen.1010495.s015
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10.1371/journal.pgen.1010495.s016
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10.1371/journal.pgen.1010495.s017
DOI:
10.1371/journal.pgen.1010495.s018
DOI:
10.1371/journal.pgen.1010495.s019
DOI:
10.1371/journal.pgen.1010495.s020
DOI:
10.1371/journal.pgen.1010495.s021
DOI:
10.1371/journal.pgen.1010495.r001
DOI:
10.1371/journal.pgen.1010495.r002
DOI:
10.1371/journal.pgen.1010495.r003
DOI:
10.1371/journal.pgen.1010495.r004
DOI:
10.1371/journal.pgen.1010495.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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