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Science
2009 Dec 18;3265960:1698-701. doi: 10.1126/science.1182372.
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The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
Knipscheer P
,
Räschle M
,
Smogorzewska A
,
Enoiu M
,
Ho TV
,
Schärer OD
,
Elledge SJ
,
Walter JC
.
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Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.
Akkari,
The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase.
2001, Pubmed
Akkari,
The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase.
2001,
Pubmed
Alpi,
Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI.
2008,
Pubmed
Ben-Yehoyada,
Checkpoint signaling from a single DNA interstrand crosslink.
2009,
Pubmed
,
Xenbase
D'Andrea,
The Fanconi anaemia/BRCA pathway.
2003,
Pubmed
Garcia-Higuera,
Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.
2001,
Pubmed
Howlett,
Biallelic inactivation of BRCA2 in Fanconi anemia.
2002,
Pubmed
Ishiai,
FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway.
2008,
Pubmed
Klein,
Breaking up just got easier to do.
2009,
Pubmed
Mirchandani,
The Fanconi anemia core complex is required for efficient point mutagenesis and Rev1 foci assembly.
2008,
Pubmed
Niedzwiedz,
The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair.
2004,
Pubmed
Patel,
Fanconi anemia and DNA replication repair.
2007,
Pubmed
Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase
Shen,
Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication.
2009,
Pubmed
Smogorzewska,
Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair.
2007,
Pubmed
Sobeck,
Fanconi anemia proteins are required to prevent accumulation of replication-associated DNA double-strand breaks.
2006,
Pubmed
,
Xenbase
Taniguchi,
S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51.
2002,
Pubmed
Wang,
Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins.
2007,
Pubmed
Wang,
Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin.
2004,
Pubmed
