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Checkpoint signaling from a single DNA interstrand crosslink.
Ben-Yehoyada M
,
Wang LC
,
Kozekov ID
,
Rizzo CJ
,
Gottesman ME
,
Gautier J
.
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DNA interstrand crosslinks (ICLs) are the most toxic lesions induced by chemotherapeutic agents such as mitomycin C and cisplatin. By covalently linking both DNA strands, ICLs prevent DNA melting, transcription, and replication. Studies on ICL signaling and repair have been limited, because these drugs generate additional DNA lesions that trigger checkpoint signaling. Here, we monitor sensing, signaling from, and repairing of a single site-specific ICL in cell-free extract derived from Xenopus eggs and in mammalian cells. Notably, we demonstrate that ICLs trigger a checkpoint response independently of origin-initiated DNA replication and uncoupling of DNA polymerase and DNA helicase. The Fanconi anemia pathway acts upstream of RPA-ATR-Chk1 to generate the ICL signal. The system also repairs ICLs in a reaction that involves extensive, error-free DNA synthesis. Repair occurs by both origin-dependent and origin-independent mechanisms. Our data suggest that cell sensitivity to crosslinking agents results from both checkpoint and DNA repair defects.
Akkari,
DNA replication is required To elicit cellular responses to psoralen-induced DNA interstrand cross-links.
2000, Pubmed
Akkari,
DNA replication is required To elicit cellular responses to psoralen-induced DNA interstrand cross-links.
2000,
Pubmed
Bergstralh,
Interstrand crosslink repair: can XPF-ERCC1 be let off the hook?
2008,
Pubmed
Byun,
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
2005,
Pubmed
,
Xenbase
Centurion,
Damage-resistant DNA synthesis in Fanconi anemia cells treated with a DNA cross-linking agent.
2000,
Pubmed
Chirnomas,
Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway.
2006,
Pubmed
Ciccia,
Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM.
2007,
Pubmed
Cipak,
The role of BRCA2 in replication-coupled DNA interstrand cross-link repair in vitro.
2006,
Pubmed
Costanzo,
An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication.
2003,
Pubmed
,
Xenbase
Dooley,
Structural studies of an oligodeoxynucleotide containing a trimethylene interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross-link.
2001,
Pubmed
Dooley,
NMR determination of the conformation of a trimethylene interstrand cross-link in an oligodeoxynucleotide duplex containing a 5'-d(GpC) motif.
2003,
Pubmed
Dronkert,
Repair of DNA interstrand cross-links.
2001,
Pubmed
Duckworth-Rysiecki,
Characterization of a simian virus 40-transformed Fanconi anemia fibroblast cell line.
1986,
Pubmed
Grompe,
Fanconi anemia and DNA repair.
2001,
Pubmed
Hanada,
The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks.
2006,
Pubmed
Henricksen,
Recombinant replication protein A: expression, complex formation, and functional characterization.
1994,
Pubmed
Henriques,
Isolation and characterization of pso mutants sensitive to photo-addition of psoralen derivatives in Saccharomyces cerevisiae.
1980,
Pubmed
Jacquemont,
The Fanconi anemia pathway and ubiquitin.
2007,
Pubmed
Kalb,
Lack of sensitivity of primary Fanconi's anemia fibroblasts to UV and ionizing radiation.
2004,
Pubmed
Kumaresan,
Deficiency in incisions produced by XPF at the site of a DNA interstrand cross-link in Fanconi anemia cells.
2007,
Pubmed
Kuraoka,
Repair of an interstrand DNA cross-link initiated by ERCC1-XPF repair/recombination nuclease.
2000,
Pubmed
Landais,
A novel cell-free screen identifies a potent inhibitor of the Fanconi anemia pathway.
2009,
Pubmed
,
Xenbase
Li,
Interstrand cross-links induce DNA synthesis in damaged and undamaged plasmids in mammalian cell extracts.
1999,
Pubmed
Lu,
Repair of psoralen interstrand cross-links in Xenopus laevis egg extracts is highly mutagenic.
2005,
Pubmed
,
Xenbase
McCulloch,
The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases.
2008,
Pubmed
McHugh,
Repair of intermediate structures produced at DNA interstrand cross-links in Saccharomyces cerevisiae.
2000,
Pubmed
McHugh,
DNA interstrand cross-link repair in the cell cycle: a critical role for polymerase zeta in G1 phase.
2006,
Pubmed
Minko,
Role for DNA polymerase kappa in the processing of N2-N2-guanine interstrand cross-links.
2008,
Pubmed
Mirchandani,
The Fanconi anemia core complex is required for efficient point mutagenesis and Rev1 foci assembly.
2008,
Pubmed
Mu,
DNA interstrand cross-links induce futile repair synthesis in mammalian cell extracts.
2000,
Pubmed
Niedernhofer,
Fanconi anemia (cross)linked to DNA repair.
2005,
Pubmed
Niedernhofer,
The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks.
2004,
Pubmed
Nojima,
Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.
2005,
Pubmed
Noll,
Formation and repair of interstrand cross-links in DNA.
2006,
Pubmed
Patel,
Fanconi anemia and DNA replication repair.
2007,
Pubmed
Perdiz,
Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells. Possible role of Dewar photoproducts in solar mutagenesis.
2000,
Pubmed
Pichierri,
Fanconi anemia proteins and the s phase checkpoint.
2004,
Pubmed
Pichierri,
DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein.
2002,
Pubmed
Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase
Robertson,
Isolation and characterization of Xenopus ATM (X-ATM): expression, localization, and complex formation during oogenesis and early development.
1999,
Pubmed
,
Xenbase
Sarkar,
DNA interstrand crosslink repair during G1 involves nucleotide excision repair and DNA polymerase zeta.
2006,
Pubmed
Shechter,
ATR and ATM regulate the timing of DNA replication origin firing.
2004,
Pubmed
,
Xenbase
Smeaton,
Distortion-dependent unhooking of interstrand cross-links in mammalian cell extracts.
2008,
Pubmed
Sobeck,
Fanconi anemia proteins are required to prevent accumulation of replication-associated DNA double-strand breaks.
2006,
Pubmed
,
Xenbase
Sobeck,
DNA structure-induced recruitment and activation of the Fanconi anemia pathway protein FANCD2.
2007,
Pubmed
,
Xenbase
Taniguchi,
S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51.
2002,
Pubmed
Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase
Wang,
Fanconi anemia proteins stabilize replication forks.
2008,
Pubmed
,
Xenbase
Wang,
Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins.
2007,
Pubmed
Wold,
Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism.
1997,
Pubmed
Wu,
FANCJ helicase defective in Fanconia anemia and breast cancer unwinds G-quadruplex DNA to defend genomic stability.
2008,
Pubmed
Ying,
The ATPase activity of MCM2-7 is dispensable for pre-RC assembly but is required for DNA unwinding.
2005,
Pubmed
,
Xenbase
Zhu,
An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication.
2006,
Pubmed
Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed
