Oncotarget

Research Papers:

R152C DNA Pol β mutation impairs base excision repair and induces cellular transformation

Ting Zhou, Feiyan Pan, Yan Cao, Ying Han, Jing Zhao, Hongfang Sun, Xiaolong Zhou, Xuping Wu, Lingfeng He, Zhigang Hu, Haoyan Chen, Binghui Shen and Zhigang Guo _

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Oncotarget. 2016; 7:6902-6915. https://doi.org/10.18632/oncotarget.6849

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Abstract

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

Correspondence to:

Haoyan Chen, e-mail: chenhaoyan@gmail.com

Binghui Shen, e-mail: bshen@coh.org

Zhigang Guo, e-mail: guozgang@gmail.com

Keywords: DNA polymerase β, BER, DNA damage, tumorigenesis, genome stability

Received: September 05, 2015     Accepted: January 03, 2016     Published: January 8, 2016

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.


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