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RECQ4 arginine methylation suppresses single-stranded DNA gap accumulation at replication forks
Ning Ma1, Xiaohua Xu2, Michael Espinoza1
1Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA 91010-3000, United States.
Nucleic Acids Research
|June 27, 2026
Summary
Protein arginine methylation modifies the RECQ4 helicase, crucial for DNA replication control. This modification ensures stable replication fork progression and genome stability, impacting cancer drug efficacy.
Area of Science:
- Molecular Biology
- Epigenetics
- DNA Replication
Background:
- Protein arginine methylation is vital for transcription and RNA processing.
- Its role in DNA replication is not well understood.
- RECQ4 helicase is involved in DNA replication.
Purpose of the Study:
- To investigate the function of protein arginine methylation in DNA replication.
- To identify the role of RECQ4 helicase modification in replication control.
Main Methods:
- Identified asymmetric dimethylarginine (aDMA) modification on RECQ4 helicase.
- Investigated the impact of aDMA modification on RECQ4 localization and function during S phase.
- Utilized site-directed mutagenesis (5RK mutant) to assess the necessity of aDMA modification for replication fidelity and cellular response to PRMT inhibition.
Main Results:
- Asymmetric dimethylarginine (aDMA) modification of RECQ4 helicase by type I PRMTs is enriched during S phase.
- aDMA modification stabilizes DNA polymerase δ association with the MCM2-7 complex, ensuring replication fork progression.
- Mutation of aDMA sites (5RK mutant) causes replication defects, G2/M arrest, and reduced sensitivity to PRMT inhibitor MS023.
Conclusions:
- Asymmetric dimethylarginine (aDMA) modification of RECQ4 is a key mechanism linking arginine methylation to DNA replication control.
- This modification is essential for stabilizing replication complexes and maintaining genome stability.
- Disruption of RECQ4 methylation affects cellular response to PRMT inhibitors, suggesting therapeutic implications.
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