UVSSA facilitates transcription-coupled repair of DNA interstrand crosslinks.

Autor: Liebau RC; Institute for Cancer Genetics, Columbia University Vangelos College of Physicians and Surgeons, New York, NY, USA., Waters C; Institute for Cancer Genetics, Columbia University Vangelos College of Physicians and Surgeons, New York, NY, USA; Agilent Technologies, La Jolla, CA 92037, USA., Ahmed A; Agilent Technologies, La Jolla, CA 92037, USA., Soni RK; Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA., Gautier J; Institute for Cancer Genetics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Genetics and Development, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Electronic address: jg130@cumc.columbia.edu.
Jazyk: angličtina
Zdroj: DNA repair [DNA Repair (Amst)] 2024 Nov; Vol. 143, pp. 103771. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.dnarep.2024.103771
Abstrakt: DNA interstrand crosslinks (ICLs) are covalent bonds between bases on opposing strands of the DNA helix which prevent DNA melting and subsequent DNA replication or RNA transcription. Here, we show that Ultraviolet Stimulated Scaffold Protein A (UVSSA) is critical for ICL repair in human cells, at least in part via the transcription coupled ICL repair (TC-ICR) pathway. Inactivation of UVSSA sensitizes human cells to ICL-inducing drugs, and delays ICL repair. UVSSA is required for replication-independent repair of a single ICL in a fluorescence-based reporter assay. UVSSA localizes to chromatin following ICL damage, and interacts with transcribing Pol II, CSA, CSB, and TFIIH. Specifically, UVSSA interaction with TFIIH is required for ICL repair and transcription inhibition blocks localization of transcription coupled repair factors to ICL damaged chromatin. Finally, UVSSA expression positively correlates with ICL-based chemotherapy resistance in human cancer cell lines. Our data strongly suggest that UVSSA is a novel ICL repair factor functioning in TC-ICR. These results provide further evidence that TC-ICR is a bona fide ICL repair mechanism that contributes to crosslinker drug resistance independently of replication-coupled ICL repair.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [DNA Repair] and was not involved in the editorial review or the decision to publish this article.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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