2. Academic Validation
  3. UVSSA facilitates transcription-coupled repair of DNA interstrand crosslinks

UVSSA facilitates transcription-coupled repair of DNA interstrand crosslinks

  • DNA Repair (Amst). 2024 Nov:143:103771. doi: 10.1016/j.dnarep.2024.103771.
Rowyn C Liebau 1,  Crystal Waters 2,  Arooba Ahmed 3,  Rajesh K Soni 4,  Jean Gautier 5
Affiliations

Affiliations

  • 1 Institute for Cancer Genetics, Columbia University Vangelos College of Physicians and Surgeons, New York, NY, USA.
  • 2 Institute for Cancer Genetics, Columbia University Vangelos College of Physicians and Surgeons, New York, NY, USA; Agilent Technologies, La Jolla, CA 92037, USA.
  • 3 Agilent Technologies, La Jolla, CA 92037, USA.
  • 4 Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
  • 5 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.
PMID: 39383571 DOI: 10.1016/j.dnarep.2024.103771
Abstract

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.

Keywords

DNA interstrand crosslink; Transcription-coupled repair; UVSSA.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z