Journal article

DNA interstrand crosslink repair and cancer

Andrew J Deans, Stephen C West

Nature Reviews Cancer | NATURE PUBLISHING GROUP | Published : 2011


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 resista..

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Awarded by Cancer Research UK

Funding Acknowledgements

This research was supported by a grant to A.J.D. and S. C. W. from the Fanconi Anaemia Research Fund. Work in S.C.W.'s laboratory is supported by the European Research Council, the Louis-Jeantet foundation, the Breast Cancer Campaign, the Swiss Bridge Foundation and Cancer Research UK.