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Nat Rev Cancer. 2011 Jun 24;11(7):467-80. doi: 10.1038/nrc3088.

DNA interstrand crosslink repair and cancer.

Author information

1
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms EN63LD, UK.

Abstract

Interstrand crosslinks (ICLs) are highly toxic DNA lesions that prevent transcription and replication by inhibiting DNA strand separation. Agents that induce ICLs were one of the earliest, and are still the most widely used, forms of chemotherapeutic drug. Only recently, however, have we begun to understand how cells repair these lesions. Important insights have come from studies of individuals with Fanconi anaemia (FA), a rare genetic disorder that leads to ICL sensitivity. Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance.

PMID:
21701511
PMCID:
PMC3560328
DOI:
10.1038/nrc3088
[Indexed for MEDLINE]
Free PMC Article

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