A Germline Polymorphism of Thymine DNA Glycosylase Induces Genomic Instability and Cellular Transformation
作者： Ashley Sjolund , Antonia A. Nemec , Nicolas Paquet , Aishwarya Prakash , Patrick Sung
DOI: 10.1371/JOURNAL.PGEN.1004753
关键词:
摘要: Thymine DNA glycosylase (TDG) functions in base excision repair, a repair pathway that acts lesion-specific manner to correct individual damaged or altered bases. TDG preferentially catalyzes the removal of thymine and uracil paired with guanine, is also active on 5-fluorouracil (5-FU) adenine guanine. The rs4135113 single nucleotide polymorphism (SNP) found 10% global population. This coding SNP results alteration Gly199 Ser. part loop responsible for stabilizing flipped abasic site pocket. Biochemical analyses indicate G199S exhibits tighter binding both its substrate product. persistent accumulation sites cells expressing leads induction double-strand breaks (DSBs). Cells variant activate damage response. When expressed cells, induces genomic instability cellular transformation. Together, these suggest individuals harboring may have increased risk developing cancer.
paperity.org
core.ac.uk 参考文章(32)
Wade S. Samowitz, Bette J. Caan, Karen W. Makar, Roger K. Wolff, Cornelia M. Ulrich, Karen Curtin, Martha L. Slattery, David J. Duggan, Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations International journal of molecular epidemiology and genetics. ,vol. 2, pp. 1- 8 ,(2011)
P Neddermann, J Jiricny, The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells. Journal of Biological Chemistry. ,vol. 268, pp. 21218- 21224 ,(1993) , 10.1016/S0021-9258(19)36913-3
Antonia A. Nemec, Drew L. Murphy, Katherine A. Donigan, Joann B. Sweasy, The S229L colon tumor-associated variant of DNA polymerase β induces cellular transformation as a result of decreased polymerization efficiency. Journal of Biological Chemistry. ,vol. 289, pp. 13708- 13716 ,(2014) , 10.1074/JBC.M114.550400
H. A. Galick, S. Kathe, M. Liu, S. Robey-Bond, D. Kidane, S. S. Wallace, J. B. Sweasy, Germ-line variant of human NTH1 DNA glycosylase induces genomic instability and cellular transformation Proceedings of the National Academy of Sciences of the United States of America. ,vol. 110, pp. 14314- 14319 ,(2013) , 10.1073/PNAS.1306752110
Jennifer Yamtich, Antonia A. Nemec, Agnes Keh, Joann B. Sweasy, A Germline Polymorphism of DNA Polymerase Beta Induces Genomic Instability and Cellular Transformation PLOS Genetics. ,vol. 8, ,(2012) , 10.1371/JOURNAL.PGEN.1003052
M. Krzesniak, D. Butkiewicz, A. Samojedny, M. Chorzy, M. Rusin, Polymorphisms in TDG and MGMT Genes - Epidemiological and Functional Study in Lung Cancer Patients from Poland Annals of Human Genetics. ,vol. 68, pp. 300- 312 ,(2004) , 10.1046/J.1529-8817.2004.00079.X
Antonia A. Nemec, Katherine A. Donigan, Drew L. Murphy, Joachim Jaeger, Joann B. Sweasy, Colon cancer-associated DNA polymerase β variant induces genomic instability and cellular transformation. Journal of Biological Chemistry. ,vol. 287, pp. 23840- 23849 ,(2012) , 10.1074/JBC.M112.362111
Tracey E Barrett, Orlando D Schärer, Renos Savva, Tom Brown, Josef Jiricny, Gregory L Verdine, Laurence H Pearl, Crystal structure of a thwarted mismatch glycosylase DNA repair complex The EMBO Journal. ,vol. 18, pp. 6599- 6609 ,(1999) , 10.1093/EMBOJ/18.23.6599
Ulrike Hardeland, Roland Steinacher, Josef Jiricny, Primo Schär, Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover The EMBO Journal. ,vol. 21, pp. 1456- 1464 ,(2002) , 10.1093/EMBOJ/21.6.1456
Miao Wen-Bin, Wang Wei, Qiu Yu-Lan, Ji Fang, Xia Zhao-Lin, Micronucleus occurrence related to base excision repair gene polymorphisms in Chinese workers occupationally exposed to vinyl chloride monomer. Journal of Occupational and Environmental Medicine. ,vol. 51, pp. 578- 585 ,(2009) , 10.1097/JOM.0B013E3181990D19