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Mechanisms of Vertebrate DNA Interstrand Cross-Link Repair

Semlow, Daniel R. and Walter, Johannes C. (2021) Mechanisms of Vertebrate DNA Interstrand Cross-Link Repair. Annual Review of Biochemistry, 90 . pp. 107-135. ISSN 0066-4154. doi:10.1146/annurev-biochem-080320-112510.

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DNA interstrand cross-links (ICLs) covalently connect the two strands of the double helix and are extremely cytotoxic. Defective ICL repair causes the bone marrow failure and cancer predisposition syndrome, Fanconi anemia, and upregulation of repair causes chemotherapy resistance in cancer. The central event in ICL repair involves resolving the cross-link (unhooking). In this review, we discuss the chemical diversity of ICLs generated by exogenous and endogenous agents. We then describe how proliferating and nonproliferating vertebrate cells unhook ICLs. We emphasize fundamentally new unhooking strategies, dramatic progress in the structural analysis of the Fanconi anemia pathway, and insights into how cells govern the choice between different ICL repair pathways. Throughout, we highlight the many gaps that remain in our knowledge of these fascinating DNA repair pathways.

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Additional Information:© 2021 Annual Reviews. Review in Advance first posted online on April 21, 2021. We apologize to colleagues whose papers we could not discuss due to space limitations. We thank Michael Seidman, Alex Wu, and Ravi Amunugama for helpful discussions and feedback. Work on ICL repair in J.C.W.’s laboratory is supported by R01HL098316. J.C.W. is an American Cancer Society Research Professor and an investigator of the Howard Hughes Medical Institute. J.C.W. is a cofounder of MoMa Therapeutics, in which he has a financial interest.
Funding AgencyGrant Number
American Cancer SocietyUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:Fanconi anemia, DNA interstrand cross-link, FANCD2, ICL, NEIL3, traverse
Record Number:CaltechAUTHORS:20210429-131108261
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Official Citation:Mechanisms of Vertebrate DNA Interstrand Cross-Link Repair. Daniel R. Semlow and Johannes C. Walter. Annual Review of Biochemistry 2021 90:1, 107-135; DOI: 10.1146/annurev-biochem-080320-112510
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108868
Deposited By: Tony Diaz
Deposited On:29 Apr 2021 20:29
Last Modified:23 Sep 2021 21:02

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