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Updated: Mar 19, 2026

A Simple, Rapid, and Quantitative Assay to Measure Repair of DNA-protein Crosslinks on Plasmids Transfected into Mammalian Cells
Published on: March 5, 2018
Involvement of translesion synthesis DNA polymerases in DNA interstrand crosslink repair
Upasana Roy1, Orlando D Schärer2
1Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
Abstract:
DNA interstrand crosslinks (ICLs) covalently join the two strands of a DNA duplex and block essential processes such as DNA replication and transcription. Several important anti-tumor drugs such as cisplatin and nitrogen mustards exert their cytotoxicity by forming ICLs. However, multiple complex pathways repair ICLs and these are thought to contribute to the development of resistance towards ICL-inducing agents. While the understanding of many aspects of ICL repair is still rudimentary, studies in recent years have provided significant insights into the pathways of ICL repair. In this perspective we review the recent advances made in elucidating the mechanisms of ICL repair with a focus on the role of TLS polymerases. We describe the emerging models for how these enzymes contribute to and are regulated in ICL repair, discuss the key open questions and examine the implications for this pathway in anti-cancer therapy.
Insights
DNA interstrand crosslinks (ICLs) block DNA replication and transcription, but cells possess complex repair pathways. Recent research highlights the crucial role of translesion synthesis (TLS) polymerases in ICL repair and cancer therapy.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- DNA interstrand crosslinks (ICLs) covalently link DNA strands, impeding replication and transcription.
- ICLs are formed by cytotoxic anti-cancer drugs like cisplatin, but resistance develops due to complex repair pathways.
Purpose of the Study:
- To review recent advances in understanding ICL repair mechanisms.
- To focus on the role and regulation of translesion synthesis (TLS) polymerases in ICL repair.
- To discuss implications for anti-cancer therapy.
Main Methods:
- Literature review of recent studies on ICL repair.
- Analysis of emerging models for TLS polymerase involvement in ICL repair.
- Discussion of regulatory mechanisms and open questions.
Main Results:
- Significant insights into ICL repair pathways have been gained recently.
- TLS polymerases play a key role in ICL repair.
- Emerging models describe how TLS polymerases contribute to and are regulated during ICL repair.
Conclusions:
- Understanding ICL repair, particularly the role of TLS polymerases, is crucial for developing effective anti-cancer therapies.
- Further research is needed to address key open questions in ICL repair pathways.
- Targeting ICL repair mechanisms may overcome resistance to ICL-inducing anti-cancer drugs.
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