Year: 2016
Type: article
Abstract: // Ting Zhou 1, * , Feiyan Pan 1, * , Yan Cao 1, * , Ying Han 1, * , Jing Zhao 1 , Hongfang Sun 1 , Xiaolong Zhou 1 , Xuping Wu 3 , Lingfeng He 1 , Zhigang Hu 1 , Haoyan Chen 2 , Binghui Shen 4 , Zhigang Guo 1 1 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China 210023 2 Division of Gastroenterology and Hepatology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 200001 3 The Second Hospital of Nanjing, the Second Affiliated Hospital of Southeast University, Nanjing, China 210003 4 Department 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: [email protected] Binghui Shen, e-mail: [email protected] Zhigang Guo, e-mail: [email protected] 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 H 2 O 2 . 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.
Source: Oncotarget
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: National Natural Science Foundation of China, Ministry of Education of the People's Republic of China, Natural Science Foundation of Jiangsu Province, National Institutes of Health, Program for New Century Excellent Talents in University, Specialized Research Fund for the Doctoral Program of Higher Education of China, National Cancer Institute
OpenAlex ID: W2237517337