DNA Damage Reversal

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R-HSA-73942
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Pathway
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Homo sapiens
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DNA damage can be directly reversed by dealkylation (Mitra and Kaina 1993). Three enzymes play a major role in reparative DNA dealkylation: MGMT, ALKBH2 and ALKBH3. MGMT dealkylates O-6-methylguanine in a suicidal reaction that inactivates the enzyme (Daniels et al. 2000, Rasimas et al. 2004, Duguid et al. 2005, Tubbs et al. 2007), while ALKBH2 and ALKBH3 dealkylate 1-methyladenine, 3-methyladenine, 3-methylcytosine and 1-ethyladenine (Duncan et al. 2002, Dango et al. 2011).

Literature References
PubMed ID Title Journal Year
10747039 Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding

Daniels, DS, Mol, CD, Arvai, AS, Kanugula, S, Pegg, AE, Tainer, JA

EMBO J. 2000
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

Tubbs, JL, Pegg, AE, Tainer, JA

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

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

Protein Sci. 2004
15964013 The structure of the human AGT protein bound to DNA and its implications for damage detection

Duguid, EM, Rice, PA, He, C

J. Mol. Biol. 2005
22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation

Dango, S, Mosammaparast, N, Sowa, ME, Xiong, LJ, Wu, F, Park, K, Rubin, M, Gygi, S, Harper, JW, Shi, Y

Mol. Cell 2011
12486230 Reversal of DNA alkylation damage by two human dioxygenases.

Duncan, T, Trewick, SC, Koivisto, P, Bates, PA, Lindahl, T, Sedgwick, B

Proc Natl Acad Sci U S A 2002
8434121 Regulation of repair of alkylation damage in mammalian genomes.

Mitra, S, Kaina, B

Prog Nucleic Acid Res Mol Biol 1993
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