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Alkylation damage repair in mammalian genomes

Conference ·
OSTI ID:10180082
; ;  [1];  [2];  [3];  [4];  [5]; ;  [6]
  1. Texas Univ. Medical Branch, Galveston, TX (United States). Sealy Center for Molecular Science
  2. Banyu Pharmaceutical Co. Research Inst., Tsukuba (Japan)
  3. NIEHS, Research Triangle, NC (United States)
  4. Oak Ridge National Lab., TN (United States)
  5. Leiden Univ. (Netherlands). Sylvius Labs.
  6. Kernforschungszentrum Karlsruhe GmbH (Germany). Inst. fuer Genetik und Toxikologie
The repair of O{sup 6} -alkylguanine in DNA involves only O{sup 6} -methyltransferase (MGMT) while the repair of N-alkylpurines requires multiple proteins including N-methylpurine-DNA glycosylase (MPG). While the biochemical properties human and mouse MGMTs are very similar, the mouse MPG removes 7-methylguanine more efficiently than the human protein. An increased level of MGMT, without a change in the level of MPG associated with gene amplification, was observed in a mouse cell line resistant to 2-chloroethyl-N-nitrosourea. In contrast, no correlation was observed between MPG level and resistance to methyl methanesulfonate in Chinese hamster ovary (CHO) cells. This result suggests a protein other than MPG limits the repair rate of N-alkylpurine in CHO cells.
Research Organization:
Oak Ridge National Lab., TN (United States)
Sponsoring Organization:
USDOE, Washington, DC (United States)
DOE Contract Number:
AC05-84OR21400
OSTI ID:
10180082
Report Number(s):
CONF-9208143--1; ON: DE93001208
Country of Publication:
United States
Language:
English