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Updated: Feb 5, 2026

Tools to Study the Role of Architectural Protein HMGB1 in the Processing of Helix Distorting, Site-specific DNA Interstrand Crosslinks
Published on: November 10, 2016
Structure-specific endonuclease activity of SNM1A enables processing of a DNA interstrand crosslink
Beverlee Buzon1,2, Ryan Grainger2, Simon Huang1
1Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster, University, Hamilton, Ontario L8N 3Z5, Canada.
Abstract:
DNA interstrand crosslinks (ICLs) covalently join opposing strands, blocking both replication and transcription, therefore making ICL-inducing compounds highly toxic and ideal anti-cancer agents. While incisions surrounding the ICL are required to remove damaged DNA, it is currently unclear which endonucleases are needed for this key event. SNM1A has been shown to play an important function in human ICL repair, however its suggested role has been limited to exonuclease activity and not strand incision. Here we show that SNM1A has endonuclease activity, having the ability to cleave DNA structures that arise during the initiation of ICL repair. In particular, this endonuclease activity cleaves single-stranded DNA. Given that unpaired DNA regions occur 5' to an ICL, these findings suggest SNM1A may act as either an endonuclease and/or exonuclease during ICL repair. This finding is significant as it expands the potential role of SNM1A in ICL repair.
Insights
SNM1A exhibits endonuclease activity, cleaving single-stranded DNA structures crucial for DNA interstrand crosslink repair. This finding expands SNM1A
Area of Science:
- Molecular Biology
- DNA Repair Mechanisms
- Cancer Therapeutics
Background:
- DNA interstrand crosslinks (ICLs) covalently link opposing DNA strands, halting replication and transcription.
- ICL-inducing agents are toxic but valuable anti-cancer therapeutics.
- Efficient DNA repair, involving specific endonucleases for incisions, is critical for ICL removal.
Purpose of the Study:
- To investigate the enzymatic activity of SNM1A in DNA interstrand crosslink repair.
- To determine if SNM1A possesses endonuclease activity beyond its known exonuclease function.
Main Methods:
- Biochemical assays to assess SNM1A's DNA cleavage activity.
- Characterization of SNM1A's ability to process DNA structures relevant to ICL repair initiation.
Main Results:
- SNM1A demonstrates endonuclease activity.
- SNM1A specifically cleaves single-stranded DNA structures.
- These structures are present 5' to an ICL during repair initiation.
Conclusions:
- SNM1A possesses endonuclease activity, capable of cleaving single-stranded DNA.
- This activity suggests SNM1A plays a direct role in initiating DNA interstrand crosslink repair incisions.
- The findings expand the known functions of SNM1A in the human ICL repair pathway.
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