A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2 Journal Article

   

Authors:	Schlacher, K.; Wu, H.; Jasin, M.
Article Title:	A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2
Abstract:	Genes mutated in patients with Fanconi anemia (FA) interact with the DNA repair genes BRCA1 and BRCA2/FANCD1 to suppress tumorigenesis, but the molecular functions ascribed to them cannot fully explain all of their cellular roles. Here, we show a repair-independent requirement for FA genes, including FANCD2, and BRCA1 in protecting stalled replication forks from degradation. Fork protection is surprisingly rescued in FANCD2-deficient cells by elevated RAD51 levels or stabilized RAD51 filaments. Moreover, FANCD2-mediated fork protection is epistatic with RAD51 functions, revealing an unanticipated fork protection pathway that connects FA genes to RAD51 and the BRCA1/2 breast cancer suppressors. Collective results imply a unified molecular mechanism for repair-independent functions of FA, RAD51, and BRCA1/2 proteins in preventing genomic instability and suppressing tumorigenesis. © 2012 Elsevier Inc..
Keywords:	controlled study; nonhuman; dna replication; animal cell; mouse; animal tissue; breast cancer; protein degradation; brca1 protein; brca2 protein; carcinogenesis; ubiquitination; genomic instability; genes, brca1; genes, brca2; cell line, transformed; dna binding; rad51 protein; fanconi anemia; gene replication; fanconi anemia group d2 protein; rad51 recombinase; genetic epistasis
Journal Title:	Cancer Cell
Volume:	22
Issue:	1
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2012-07-10
Start Page:	106
End Page:	116
Language:	English
DOI:	10.1016/j.ccr.2012.05.015
PROVIDER:	scopus
PUBMED:	22789542
PMCID:	PMC3954744
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84863753191&partnerID=40&md5=016d9b08bad371aa419d7cd24d76a7a1
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 1 August 2012" - "CODEN: CCAEC" - "Source: Scopus"

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