MGMT/hAGT mediated DNA Damage Reversal

Stable Identifier
R-HSA-73892
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
MGMT/hAGT mediated DNA Damage Reversal
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
MGMT, just like its E.coli homolog Ada, is an O-6-methylguanine transferase (Lindahl et al. 1983, Moore et al. 1994) that removes the methyl group from the guanine and transfers it to the cysteine residue at position 145 on the protein itself. MGMT thus methylated is not regenerated, as the S-methylcysteine is very stable. This is an energetically expensive approach to DNA repair as one entire protein molecule is sacrificed per lesion that is corrected in this manner (Rasimas et al. 2004, Tubbs et al. 2007, Mitra and Kaina 1993).
Literature References
PubMed ID Title Journal Year
17485252 DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy

Pegg, AE, Tainer, JA, Tubbs, JL

DNA Repair (Amst.) 2007
14691244 Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase

Rasimas, JJ, Pegg, AE, Ropson, IJ, Dalessio, PA, Fried, MG

Protein Sci. 2004
8156986 Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli

Dodson, EJ, Moore, MH, Demple, B, Gulbis, JM, Moody, PC

EMBO J. 1994
6765195 Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase

Demple, B, Lindahl, T, Robins, P

EMBO J. 1982
8434121 Regulation of repair of alkylation damage in mammalian genomes.

Mitra, S, Kaina, B

Prog Nucleic Acid Res Mol Biol 1993
Participants
Input
Output
Participates
as an event of
Event Information
Go Biological Process
DNA alkylation repair (0006307)
Catalyst Activity

methylated-DNA-[protein]-cysteine S-methyltransferase activity of MGMT:Zn2+:6-OMeG-dsDNA [nucleoplasm]

Physical Entity
MGMT:Zn2+:6-OMeG-dsDNA [nucleoplasm] (Homo sapiens)
Activity
methylated-DNA-[protein]-cysteine S-methyltransferase activity (GO:0003908)
Authored
Pegg, AE  (2004-02-04)
Reviewed
Joshi-Tope, G  (2004-02-04)
Gillespie, ME  (2015-02-06)
Created
Pegg, AE  (2004-02-04)
Cite Us!