SAMHD1-mediated dNTP degradation is required for efficient DNA repair during antibody class switch recombination.

The EMBO Journal
Afzal HusainNasim A Begum

Abstract

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1), a dNTP triphosphohydrolase, regulates the levels of cellular dNTPs through their hydrolysis. SAMHD1 protects cells from invading viruses that depend on dNTPs to replicate and is frequently mutated in cancers and Aicardi-Goutières syndrome, a hereditary autoimmune encephalopathy. We discovered that SAMHD1 localizes at the immunoglobulin (Ig) switch region, and serves as a novel DNA repair regulator of Ig class switch recombination (CSR). Depletion of SAMHD1 impaired not only CSR but also IgH/c-Myc translocation. Consistently, we could inhibit these two processes by elevating the cellular nucleotide pool. A high frequency of nucleotide insertion at the break-point junctions is a notable feature in SAMHD1 deficiency during activation-induced cytidine deaminase-mediated genomic instability. Interestingly, CSR induced by staggered but not blunt, double-stranded DNA breaks was impaired by SAMHD1 depletion, which was accompanied by enhanced nucleotide insertions at recombination junctions. We propose that SAMHD1-mediated dNTP balance regulates dNTP-sensitive DNA end-processing enzyme and promotes CSR and aberrant genomic rearrangements by suppressing...Continue Reading

References

Nov 18, 1983·Science·P LederR Taub
May 26, 1998·The EMBO Journal·R CasellasM C Nussenzweig
Oct 19, 2001·Oncogene·R Küppers, R Dalla-Favera
May 7, 2003·The Journal of Experimental Medicine·Il-mi OkazakiTasuku Honjo
Jul 2, 2004·Nature Reviews. Immunology·Jayanta Chaudhuri, Frederick W Alt
Jan 20, 2005·The Journal of Experimental Medicine·Qiang Pan-HammarströmMichael R Ehrenstein
Aug 17, 2005·The Journal of Experimental Medicine·Carol E SchraderJanet Stavnezer
Dec 11, 2007·Nature Genetics·Laura PasqualucciRiccardo Dalla-Favera
Dec 26, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Holger BabbePhilip Leder
Oct 7, 2009·Journal of Bioscience and Bioengineering·Akemi Hoshino, Hodaka Fujii
Dec 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andre StanlieNasim A Begum
Nov 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Maki KobayashiTasuku Honjo
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Cristian BoboilaBjoern Schwer
Mar 21, 2012·Advances in Cancer Research·Tasuku HonjoHitoshi Nagaoka
Sep 14, 2012·Nature Medicine·Hanna-Mari BaldaufOliver T Keppler
Sep 15, 2012·Annual Review of Pathology·Davide F Robbiani, Michel C Nussenzweig
Feb 1, 2013·The Journal of Biological Chemistry·Natalia BeloglazovaAlexander F Yakunin
Feb 2, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Victoria TünglerMin Ae Lee-Kirsch
Jul 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Elisa FranzolinVera Bianchi
Sep 14, 2013·Science·David Tarlinton, Kim Good-Jacobson
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ashraf S YousifNasim A Begum
May 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Masahiro OnozawaPeter D Aplan
Jul 21, 2014·Nature Medicine·Jeongmin RyooKwangseog Ahn
Aug 8, 2014·Nature Protocols·Georg KustatscherJuri Rappsilber
Sep 5, 2014·Nature·Havva KeskinFrancesca Storici
Oct 3, 2014·PLoS Genetics·Matthew J YousefzadehRichard D Wood
Nov 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jianliang XuMaki Kobayashi

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Citations

Dec 1, 2020·Trends in Biochemical Sciences·Tannishtha SahaMichela Di Virgilio
Feb 17, 2021·Nucleic Acids Research·Ekaterina AkimovaRoland Geisberger
Apr 21, 2021·The CRISPR Journal·Hirotaka FujitaHodaka Fujii
Sep 5, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kerstin SchottRenate König
Dec 12, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·BradleyS BarrettMario L Santiago

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