Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base-excision repair
作者： Ya-Qiang Li , Ping-Zhu Zhou , Xiu-Dan Zheng , Colum P. Walsh , Guo-Liang Xu
DOI: 10.1093/NAR/GKL1052
关键词: MBD4 、 DNA repair 、 Deamination 、 DNA glycosylase 、 Biology 、 Thymine-DNA glycosylase 、 Base excision repair 、 Biochemistry 、 DNA methyltransferase 、 Very short patch repair
摘要: While methylcytosines serve as the fifth base encoding epigenetic information, they are also a dangerous endogenous mutagen due to their intrinsic instability. Methylcytosine undergoes spontaneous deamination, at rate much higher than cytosine, generate thymine. In mammals, two repair enzymes, thymine DNA glycosylase (TDG) and methyl-CpG binding domain 4 (MBD4), have evolved counteract mutagenic effect of methylcytosines. Both recognize G/T mismatches arising from methylcytosine deamination initiate base-excision that corrects them G/C pairs. However, mechanism by which methylation status repaired cytosines is restored has remained unknown. We show here methyltransferase Dnmt3a interacts with TDG. PWWP catalytic able mediate interaction TDG its N-terminus. The affects enzymatic activity both proteins: positively regulates TDG, while inhibits in vitro. These data suggest mechanistic link between remethylation sites affected deamination.
oup.com
core.ac.uk
elsevier.com
ulster.ac.uk
paperity.org参考文章(50)
Peter A. Jones, Stephen B. Baylin, The fundamental role of epigenetic events in cancer Nature Reviews Genetics. ,vol. 3, pp. 415- 428 ,(2002) , 10.1038/NRG816
Wolf Reik, Gavin Kelsey, Jörn Walter, Dissecting de novo methylation. Nature Genetics. ,vol. 23, pp. 380- 382 ,(1999) , 10.1038/70476
Ulrike Hardeland, Marl Bentele, Teresa Lettieri, Roland Steinacher, Josef Jiricny, Primo Schär, Thymine DNA glycosylase Progress in Nucleic Acid Research and Molecular Biology. ,vol. 68, pp. 235- 253 ,(2001) , 10.1016/S0079-6603(01)68103-0
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
Brian Hendrich, Ulrike Hardeland, Huck-Hui Ng, Josef Jiricny, Adrian Bird, The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites Nature. ,vol. 401, pp. 301- 304 ,(1999) , 10.1038/45843
Déborah Bourc'his, Guo-Liang Xu, Chyuan-Sheng Lin, Brooke Bollman, Timothy H Bestor, Dnmt3L and the Establishment of Maternal Genomic Imprints Science. ,vol. 294, pp. 2536- 2539 ,(2001) , 10.1126/SCIENCE.1065848
Ashok S. Bhagwat, Margaret Lieb, Cooperation and competition in mismatch repair: very short-patch repair and methyl-directed mismatch repair in Escherichia coli. Molecular Microbiology. ,vol. 44, pp. 1421- 1428 ,(2002) , 10.1046/J.1365-2958.2002.02989.X
C. P. Walsh, G. L. Xu, Cytosine methylation and DNA repair Current Topics in Microbiology and Immunology. ,vol. 301, pp. 283- 315 ,(2006) , 10.1007/3-540-31390-7_11
Rudolf Jaenisch, Adrian Bird, Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals Nature Genetics. ,vol. 33, pp. 245- 254 ,(2003) , 10.1038/NG1089
Marc Tini, Arndt Benecke, Soo-Joong Um, Joseph Torchia, Ronald M Evans, Pierre Chambon, Association of CBP/p300 Acetylase and Thymine DNA Glycosylase Links DNA Repair and Transcription Molecular Cell. ,vol. 9, pp. 265- 277 ,(2002) , 10.1016/S1097-2765(02)00453-7