Human POLB gene is mutated in high percentage of colorectal tumors.

The Journal of Biological Chemistry
Katherine A DoniganJoann B Sweasy

Abstract

Previous small scale sequencing studies have indicated that DNA polymerase β (pol β) variants are present on average in 30% of human tumors of varying tissue origin. Many of these variants have been shown to have aberrant enzyme function in vitro and to induce cellular transformation and/or genomic instability in vivo, suggesting that their presence is associated with tumorigenesis or its progression. In this study, the human POLB gene was sequenced in a collection of 134 human colorectal tumors and was found to contain coding region mutations in 40% of the samples. The variants map to many different sites of the pol β protein and are not clustered. Many variants are nonsynonymous amino acid substitutions predicted to affect enzyme function. A subset of these variants was found to have reduced enzyme activity in vitro and failed to fully rescue pol β-deficient cells from methylmethane sulfonate-induced cytotoxicity. Tumors harboring variants with reduced enzyme activity may have compromised base excision repair function, as evidenced by our methylmethane sulfonate sensitivity studies. Such compromised base excision repair may drive tumorigenesis by leading to an increase in mutagenesis or genomic instability.

References

Jan 1, 1993·Annual Review of Biochemistry·K A Johnson
Nov 1, 1995·Human Molecular Genetics·A L BørresenR D Kolodner
Jan 1, 1997·Human Molecular Genetics·M G DunlopB Vogelstein
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·N Bhattacharyya, S Banerjee
Jun 17, 1998·The Journal of Biological Chemistry·R PrasadS H Wilson
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
Jul 10, 2001·Life Sciences·N BhattacharyyaS Banerjee
Jul 27, 2001·Biochemistry·N Bhattacharyya, S Banerjee
Jan 31, 2002·Nature Genetics·Nada Al-TassanJeremy P Cheadle
May 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stanton L Gerson
Feb 8, 2003·Current Opinion in Genetics & Development·Josef Jiricny, Giancarlo Marra
Dec 31, 2003·Cell·Benjamin P LewisChristopher B Burge
Apr 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Tieming LangJoann B Sweasy
May 25, 2004·Science·Zhenghe WangVictor E Velculescu
Jul 29, 2004·Cell Cycle·Daniela StarcevicJoann B Sweasy
Sep 24, 2004·RNA·Marc RehmsmeierRobert Giegerich
Oct 7, 2004·Environmental and Molecular Mutagenesis·Mark MeyersDavid A Boothman
Sep 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Joann B SweasyShibani Dalal
Mar 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jordan M CumminsVictor E Velculescu
Apr 21, 2006·The FEBS Journal·Jung-Suk Sung, Bruce Demple
Sep 9, 2006·Science·Tobias SjöblomVictor E Velculescu
Mar 9, 2007·Nature·Christopher GreenmanMichael R Stratton
Aug 21, 2007·Biology of the Cell·J Ross Buchan, Ian Stansfield
Nov 28, 2007·Nucleic Acids Research·Shibani DalalJoann B Sweasy
Jun 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fiona GintyMichael C Montalto
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Dec 9, 2010·Cancer Causes & Control : CCC·Kaori ShimaShuji Ogino
Apr 2, 2011·Journal of the American Chemical Society·Drew L MurphyJoann B Sweasy
Sep 21, 2011·Molecular and Cellular Biology·Ian D OdellDavid S Pederson
May 11, 2012·The Journal of Biological Chemistry·Antonia A NemecJoann B Sweasy

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Citations

May 11, 2012·The Journal of Biological Chemistry·Antonia A NemecJoann B Sweasy
Jun 14, 2013·Nucleic Acids Research·Anbarasi KothandapaniSteve M Patrick
Feb 13, 2014·Journal of the American Chemical Society·Dumitru ArianMarc M Greenberg
Oct 16, 2012·Environmental and Molecular Mutagenesis·Marc J Prindle, Lawrence A Loeb
Aug 6, 2013·Environmental and Molecular Mutagenesis·Parvathi CharyR Stephen Lloyd
Oct 27, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·Kalyani KhanraNandan Bhattacharya
Jun 12, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Min LiGuoqiang Zhao
Mar 27, 2012·Journal of Molecular Biology·Rebecca B BerlowJ Patrick Loria
Mar 25, 2014·Biochemistry·Thomas W KirbyRobert E London
Nov 20, 2014·Nature·Bret D FreudenthalSamuel H Wilson
Sep 3, 2016·Genes·Elisa MentegariEmmanuele Crespan
Dec 14, 2016·Nucleic Acids Research·Thomas W KirbyRobert E London
Mar 29, 2018·The Journal of Biological Chemistry·Yesenia RodriguezMichael J Smerdon
Oct 18, 2013·The Journal of Biological Chemistry·Brian E EckenrothSylvie Doublié
Jun 18, 2020·Frontiers in Immunology·Maria StratigopoulouJeroen E J Guikema
Apr 2, 2013·The Journal of Biological Chemistry·Yesenia Rodriguez, Michael J Smerdon
Apr 2, 2016·The Journal of Biological Chemistry·Yesenia RodriguezMichael J Smerdon
Oct 28, 2019·Mutagenesis·Roberto Silvestri, Stefano Landi
Sep 28, 2014·The Journal of Biological Chemistry·William A BeardSamuel H Wilson
Jan 12, 2017·Molecular Cancer Research : MCR·Antonia A NemecJoann B Sweasy
May 21, 2021·Journal of the American Chemical Society·Shelby C YuhasMarc M Greenberg
Jul 10, 2021·ACS Chemical Biology·Shelby C YuhasMarc M Greenberg
Jul 3, 2021·Chembiochem : a European Journal of Chemical Biology·Shelby C YuhasMarc M Greenberg
Aug 26, 2017·Chemical Research in Toxicology·Maroof K Zafar, Robert L Eoff
Oct 26, 2021·The Journal of Biological Chemistry·Yuan XueStephen R Quake

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