title: R152C DNA Pol β mutation impairs base excision repair and induces cellular transformation.
abstract: DNA polymerase β (Pol β) is a key enzyme in DNA base excision repair (BER), a pathway that maintains genome integrity and stability. Pol β mutations have been detected in various types of cancers, suggesting a possible linkage between Pol β mutations and cancer. However, it is not clear whether and how Pol β mutations cause cancer onset and progression. In the current work, we show that a substitution mutation, R152C, impairs Pol β polymerase activity and BER efficiency. Cells harboring Pol β R152C are sensitive to the DNA damaging agents methyl methanesulfonate (MMS) and H2O2. Moreover, the mutant cells display a high frequency of chromatid breakages and aneuploidy and also form foci. Taken together, our data indicate that Pol β R152C can drive cellular transformation.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Pan
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The Second Hospital of Nanjing, The Second Affiliated Hospital of Southeast University, Nanjing, China 210003.
authors.forename: Xuping
authors.initials: X
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: He
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Division of Gastroenterology and Hepatology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 200001.
authors.forename: Haoyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA 91010.
authors.forename: Binghui
authors.initials: B
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation
chemical_list: D019951:DNA Polymerase beta
keywords: BER; DNA damage; DNA polymerase β; genome stability; tumorigenesis