Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The tumor suppressor protein BRCA1 promotes homologous recombination (HR), a high-fidelity mechanism to repair DNA double-strand breaks (DSBs) that arise during normal replication and in response to DNA-damaging agents. Recent genetic experiments indicate that BRCA1 also performs an HR-independent function during the repair of DNA interstrand crosslinks (ICLs). Here we show that BRCA1 is required to unload the CMG helicase complex from chromatin after replication forks collide with an ICL. Eviction of the stalled helicase allows leading strands to be extended toward the ICL, followed by endonucleolytic processing of the crosslink, lesion bypass, and DSB repair. Our results identify BRCA1-dependent helicase unloading as a critical, early event in ICL repair.
Bekker-Jensen,
Assembly and function of DNA double-strand break repair foci in mammalian cells.
2010, Pubmed
Bekker-Jensen,
Assembly and function of DNA double-strand break repair foci in mammalian cells.
2010,
Pubmed Bhattacharyya,
The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin.
2000,
Pubmed Borodovsky,
A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14.
2001,
Pubmed Bouwman,
53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers.
2010,
Pubmed Bridge,
The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair.
2005,
Pubmed Brzovic,
Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.
2001,
Pubmed Bunting,
BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair.
2012,
Pubmed Bunting,
53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks.
2010,
Pubmed Chalasani,
Differential chemotherapeutic sensitivity for breast tumors with "BRCAness": a review.
2013,
Pubmed Cheng,
DNA polymerase epsilon: aphidicolin inhibition and the relationship between polymerase and exonuclease activity.
1993,
Pubmed Choudhury,
Ubiquitination and proteasomal degradation of the BRCA1 tumor suppressor is regulated during cell cycle progression.
2004,
Pubmed De Leeneer,
Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing.
2012,
Pubmed Dimova,
APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1.
2012,
Pubmed
,
Xenbase Enoiu,
Construction of plasmids containing site-specific DNA interstrand cross-links for biochemical and cell biological studies.
2012,
Pubmed Errico,
Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts.
2007,
Pubmed
,
Xenbase Fang,
Distinct roles of cdk2 and cdc2 in RP-A phosphorylation during the cell cycle.
1993,
Pubmed
,
Xenbase Fu,
Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase.
2011,
Pubmed
,
Xenbase Fukui,
Distinct roles of DNA polymerases delta and epsilon at the replication fork in Xenopus egg extracts.
2004,
Pubmed
,
Xenbase Garcia-Higuera,
Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
2001,
Pubmed Greenberg,
Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes.
2006,
Pubmed Hashizume,
The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation.
2001,
Pubmed Holstein,
Quantitative amplification of single-stranded DNA.
2012,
Pubmed Ilves,
Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins.
2010,
Pubmed Jensen,
Purified human BRCA2 stimulates RAD51-mediated recombination.
2010,
Pubmed Joukov,
The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly.
2006,
Pubmed
,
Xenbase Joukov,
Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development.
2001,
Pubmed
,
Xenbase Kass,
Collaboration and competition between DNA double-strand break repair pathways.
2010,
Pubmed Kim,
Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway.
2012,
Pubmed Klein Douwel,
XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4.
2014,
Pubmed
,
Xenbase Knipscheer,
The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
2009,
Pubmed
,
Xenbase Kochaniak,
Proliferating cell nuclear antigen uses two distinct modes to move along DNA.
2009,
Pubmed
,
Xenbase Kubota,
A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication.
2003,
Pubmed
,
Xenbase Lebofsky,
DNA replication in nucleus-free Xenopus egg extracts.
2009,
Pubmed
,
Xenbase Liu,
Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA.
2010,
Pubmed Long,
Mechanism of RAD51-dependent DNA interstrand cross-link repair.
2011,
Pubmed
,
Xenbase McHugh,
Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance.
2001,
Pubmed Muniandy,
DNA interstrand crosslink repair in mammalian cells: step by step.
2010,
Pubmed Narod,
BRCA1 and BRCA2: 1994 and beyond.
2004,
Pubmed Niedzwiedz,
The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair.
2004,
Pubmed Nijman,
The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway.
2005,
Pubmed Oestergaard,
Deubiquitination of FANCD2 is required for DNA crosslink repair.
2007,
Pubmed Ohashi,
Fanconi anemia complementation group D2 (FANCD2) functions independently of BRCA2- and RAD51-associated homologous recombination in response to DNA damage.
2005,
Pubmed Pinder,
Reading, writing, and repair: the role of ubiquitin and the ubiquitin-like proteins in DNA damage signaling and repair.
2013,
Pubmed Qing,
The epistatic relationship between BRCA2 and the other RAD51 mediators in homologous recombination.
2011,
Pubmed Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase Schlegel,
BRCA1 promotes induction of ssDNA by ionizing radiation.
2006,
Pubmed Silver,
Mechanisms of BRCA1 tumor suppression.
2012,
Pubmed Smogorzewska,
Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair.
2007,
Pubmed Vandenberg,
BRCA1-independent ubiquitination of FANCD2.
2003,
Pubmed Waga,
DNA polymerase epsilon is required for coordinated and efficient chromosomal DNA replication in Xenopus egg extracts.
2001,
Pubmed
,
Xenbase Walter,
Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.
2000,
Pubmed
,
Xenbase Wang,
Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response.
2007,
Pubmed Wang,
Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin.
2004,
Pubmed Wang,
BRCA1 tumor suppressor network: focusing on its tail.
2012,
Pubmed Westermark,
BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks.
2003,
Pubmed Wu,
The role of BRCA1 in DNA damage response.
2010,
Pubmed Yan,
RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites.
2008,
Pubmed Yun,
CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle.
2009,
Pubmed Zhang,
PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2.
2009,
Pubmed Zhang,
The role of BRCA1 in homologous recombination repair in response to replication stress: significance in tumorigenesis and cancer therapy.
2013,
Pubmed
