Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links

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Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links

Cells deficient in the Werner syndrome protein (WRN) or BRCA1 are hypersensitive to DNA interstrand cross-links (ICLs), whose repair requires nucleotide excision repair (NER) and homologous recombination (HR). However, the roles of WRN and BRCA1 in the repair of DNA ICLs are not understood and the molecular mechanisms of ICL repair at the processing stage have not yet been established. This stu...

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Schizosaccharomyces pombe checkpoint response to DNA interstrand cross-links.

Drugs that produce covalent interstrand cross-links (ICLs) in DNA remain central to the treatment of cancer, but the cell cycle checkpoints activated by ICLs have received little attention. We have used the fission yeast, Schizosaccharomyces pombe, to elucidate the checkpoint responses to the ICL-inducing anticancer drugs nitrogen mustard and mitomycin C. First we confirmed that the repair path...

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MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links.

MERIT40 is an essential component of the RAP80 ubiquitin recognition complex that targets BRCA1 to DNA damage sites. Although this complex is required for BRCA1 foci formation, its physiologic role in DNA repair has remained enigmatic, as has its relationship to canonical DNA repair mechanisms. Surprisingly, we found that Merit40(-/-) mice displayed marked hypersensitivity to DNA interstrand cr...

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Interstrand cross-links generated by abasic sites in duplex DNA.

Abasic sites (1, Scheme 1), which are generated by hydrolysis of the glycosidic bonds connecting the heterocyclic nucleobases to the deoxyribose backbone, represent the most common type of damage suffered by genomic DNA.1 Spontaneous hydrolysis yields approximately 10,000 abasic sites per cell per day. In addition, exposure of DNA to radiation, mutagens, and anticancer drugs can lead to the gen...

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Rearrangement of interstrand cross-links into intrastrand cross-links in cis-diamminedichloroplatinum(II)-modified DNA.

In the reaction of the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP) with DNA, bifunctional intrastrand and interstrand cross-links are formed. In this work, we show that at 37 degrees C interstrand cross-links (ICL) are labile and rearrange into intrastrand cross-links. The ICL instability was first studied with a 10 base pairs (bp) double-stranded oligonucleotide containing a uni...

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ژورنال

عنوان ژورنال: Nucleic Acids Research

سال: 2006

ISSN: 0305-1048,1362-4962

DOI: 10.1093/nar/gkl362