SAMHD1 Restrains Aberrant Nucleotide Insertions at Repair Junctions Generated by DNA End Joining

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2021 Feb 16

PMID 33591315

Citations 12

Authors

Ekaterina Akimova

Franz Josef Gassner

Maria Schubert

Stefan Rebhandl

Claudia Arzt

Stefanie Rauscher

Vanessa Tober

Nadja Zaborsky

Richard Greil

Roland Geisberger

Affiliations

Soon will be listed here.

Abstract

Aberrant end joining of DNA double strand breaks leads to chromosomal rearrangements and to insertion of nuclear or mitochondrial DNA into breakpoints, which is commonly observed in cancer cells and constitutes a major threat to genome integrity. However, the mechanisms that are causative for these insertions are largely unknown. By monitoring end joining of different linear DNA substrates introduced into HEK293 cells, as well as by examining end joining of CRISPR/Cas9 induced DNA breaks in HEK293 and HeLa cells, we provide evidence that the dNTPase activity of SAMHD1 impedes aberrant DNA resynthesis at DNA breaks during DNA end joining. Hence, SAMHD1 expression or low intracellular dNTP levels lead to shorter repair joints and impede insertion of distant DNA regions prior end repair. Our results reveal a novel role for SAMHD1 in DNA end joining and provide new insights into how loss of SAMHD1 may contribute to genome instability and cancer development.

Citing Articles

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