R152C DNA Pol β mutation impairs base excision repair and induces cellular transformation
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Ting Zhou1,*, Feiyan Pan1,*, Yan Cao1,*, Ying Han1,*, Jing Zhao1, Hongfang Sun1, Xiaolong Zhou1, Xuping Wu3, Lingfeng He1, Zhigang Hu1, Haoyan Chen2, Binghui Shen4, Zhigang Guo1
1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023
2Division of Gastroenterology and Hepatology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 200001
3The Second Hospital of Nanjing, the Second Affiliated Hospital of Southeast University, Nanjing, China 210003
4Department of Cancer Genetics and Epigenetics, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA 91010
*These authors have contributed equally to this work
Haoyan Chen, e-mail: email@example.com
Binghui Shen, e-mail: firstname.lastname@example.org
Zhigang Guo, e-mail: email@example.com
Keywords: DNA polymerase β, BER, DNA damage, tumorigenesis, genome stability
Received: September 05, 2015 Accepted: January 03, 2016 Published: January 8, 2016
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.
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