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Cell September 19, 2008; 134 (6): 969-80.

Mechanism of replication-coupled DNA interstrand crosslink repair.

Räschle M , Knipscheer P , Knipsheer P , Enoiu M , Angelov T , Sun J , Griffith JD , Ellenberger TE , Schärer OD , Walter JC .

DNA interstrand crosslinks (ICLs) are toxic DNA lesions whose repair occurs in the S phase of metazoans via an unknown mechanism. Here, we describe a cell-free system based on Xenopus egg extracts that supports ICL repair. During DNA replication of a plasmid containing a site-specific ICL, two replication forks converge on the crosslink. Subsequent lesion bypass involves advance of a nascent leading strand to within one nucleotide of the ICL, followed by incisions, translesion DNA synthesis, and extension of the nascent strand beyond the lesion. Immunodepletion experiments suggest that extension requires DNA polymerase zeta. Ultimately, a significant portion of the input DNA is fully repaired, but not if DNA replication is blocked. Our experiments establish a mechanism for ICL repair that reveals how this process is coupled to DNA replication.

PubMed ID: 18805090
PMC ID: PMC2748255
Article link: Cell
Grant support: [+]
Genes referenced: ercc4 mus81

Article Images: [+] show captions
Akkari, 2000, Pubmed [+]

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