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Updated: Jan 12, 2026
In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
Deubiquitinases in DNA damage repair: Implication and mechanism in cancer
Leilei Li1, Xinyu Gu2, Tao Zhang2
1School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, Henan, 455000, China.
Abstract:
DNA damage response (DDR), a highly complicated regulatory network that detects and repairs DNA lesions, serves as an indispensable guardian of genomic integrity. Targeting aberrant DNA repair pathway has emerged as a promising therapeutic approach for cancer, which includes double-strand break repair (DSBR), nucleotide and base excision repair (NER/BER) and mismatch repair (MMR). Elucidating precise molecular mechanisms of DNA damage repair and their synthetic lethal effects will facilitate the development of novel therapeutic targets and strategies for cancer. Deubiquitinases (DUBs) modulate the subcellular localization, protein activity and stability of DDR molecules, thereby playing a critical role in dynamically orchestrating DNA damage repair process. Furthermore, DUBs are highly attractive drug targets in cancer therapies due to their catalytic domains. This review provides a comprehensive overview of the multifaceted roles and mechanisms of DUBs in DNA damage responses and their anticancer potential.
Insights
Deubiquitinases (DUBs) are crucial regulators of the DNA damage response (DDR) network. Targeting DUBs offers a promising strategy for developing novel anticancer therapies by exploiting their role in DNA repair pathways.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The DNA damage response (DDR) network is essential for maintaining genomic integrity.
- Aberrant DNA repair pathways are hallmarks of cancer, making them therapeutic targets.
- Deubiquitinases (DUBs) are enzymes that regulate DDR by modifying key proteins.
Purpose of the Study:
- To provide a comprehensive overview of the roles and mechanisms of DUBs in DNA damage responses.
- To explore the potential of DUBs as therapeutic targets for cancer treatment.
Main Methods:
- Literature review of studies on DUBs and DNA damage repair.
- Analysis of the mechanisms by which DUBs influence DDR pathways.
- Evaluation of DUBs as drug targets in cancer therapy.
Main Results:
- DUBs dynamically orchestrate DNA damage repair by modulating DDR molecule localization, activity, and stability.
- Specific DUBs play critical roles in various DNA repair pathways, including double-strand break repair (DSBR), nucleotide and base excision repair (NER/BER), and mismatch repair (MMR).
- The catalytic domains of DUBs make them attractive targets for anticancer drug development.
Conclusions:
- DUBs are multifaceted regulators of DDR with significant anticancer potential.
- Understanding DUBs' mechanisms in DNA repair can lead to novel therapeutic strategies for cancer.
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