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The Fanconi anemia pathway in replication stress and DNA crosslink repair

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Abstract

Interstand crosslinks (ICLs) are DNA lesions where the bases of opposing DNA strands are covalently linked, inhibiting critical cellular processes such as transcription and replication. Chemical agents that generate ICLs cause chromosomal abnormalities including breaks, deletions and rearrangements, making them highly genotoxic compounds. This toxicity has proven useful for chemotherapeutic treatment against a wide variety of cancer types. The majority of our understanding of ICL repair in humans has been uncovered through analysis of the rare genetic disorder Fanconi anemia, in which patients are extremely sensitive to crosslinking agents. Here, we discuss recent insights into ICL repair gained using new repair assays and highlight the role of the Fanconi anemia repair pathway during replication stress.

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Abbreviations

FA:

Fanconi anemia

USP1:

Ubiquitin-specific protease 1

DUBs:

Deubiquitinating enzymes

PCNA:

Proliferating cell nuclear antigen

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  1. Mathew J. K. Jones

    Present address: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

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  1. Department of Biochemistry, New York University School of Medicine, 550 First Ave., MSB 399, New York, NY, 10016, USA

    Mathew J. K. Jones & Tony T. Huang

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Correspondence to Tony T. Huang.

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Jones, M.J.K., Huang, T.T. The Fanconi anemia pathway in replication stress and DNA crosslink repair. Cell. Mol. Life Sci. 69, 3963–3974 (2012). https://doi.org/10.1007/s00018-012-1051-0

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  • DOI: https://doi.org/10.1007/s00018-012-1051-0

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