O6 methyl-guanine methyltransferase DNA Research Progress.docVIP

 PAGE \* MERGEFORMAT 19 O6 methyl-guanine methyltransferase DNA Research Progress Author: ZHU Ling-Dong Cai Long Yuan Village Keywords: O6  methyl-guanine  DNA  methyltransferase MGMT DNA repair enzyme tumor 0 Introduction O6  methyl-guanine  DNA  methyltransferase (O6  methylguanine  DNA methyltransferase, MGMT) is a highly efficient direct DNA repair enzymes can repair DNA sequence of the 6  O  methyl-guanine (O6  methylguanine, O6  mG) injury, is found in human cells so far the only repair the damage methyltransferase. 1 MGMT Overview 1.1 The genetic structure of the human MGMT (hMGMT) gene located in 10q26, full-length 170 kb, containing 5 exons and 4 introns. GC-rich sequence of its promoter, the lack of TATA boxes and CAAT boxes. Have been identified cis-acting elements are CpG islands in the 6 Spl sites, two glucocorticoid response elements (GRE), AP  1 and AP  2 elements. 1.2 gene polymorphism with genetic polymorphism of the phenomenon of MGMT. Imai, etc. found in MGMT gene exon 5 codon 160 at GGA → AGA, glycine is converted to arginine (G160R), 15% of Japanese existence of such polymorphisms, the Caucasus and the United States in both population found that the polymorphism. Deng and other found a human MGMT gene missense polymorphism occurs in exon 5, the first 143 codon, ATC → GTC, isoleucine is converted to Screenshots acid (1 143V). 1.3 Protein Structure hMGMT as a single peptide structure, containing 207 amino acid residues, relative molecular weight of 23 000, there are 13 conserved amino acids. Known in all of the MGMT, are there “ Pro144  Cys145  His146  Arg147  ( PHCR )” the basic structure, form part of the dynamic center. Cys145 is the most critical amino acids, and its methyl  SH directly involved in the transfer role, combined with the formation of S  methyl-alkyl cysteine. His146, Arg147 promote Cys145 thiol ions produced are conducive to Cys145 methyl-bin