Structure-specific endonuclease activity of SNM1A enables processing of a DNA interstrand crosslink

Nucleic Acids Research
Beverlee BuzonMurray Junop

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.

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Citations

Jan 27, 2020·Environmental and Molecular Mutagenesis·Julie Rageul, Hyungjin Kim
Jan 14, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eva-Maria Dürr, Joanna F McGouran
Feb 14, 2021·Journal of Huntington's Disease·Amit L DeshmukhChristopher E Pearson
Apr 20, 2021·ACS Omega·Beverlee BuzonMurray Junop
Jul 16, 2021·Frontiers in Cell and Developmental Biology·Qiuzhen LiLajos Haracska

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Methods Mentioned

BETA
PCR

Software Mentioned

ImageLab
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