Reactome | DNA Damage Reversal

DNA Damage Reversal

Stable Identifier

R-HSA-73942

DOI

10.3180/REACT_127.1

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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
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
10747039	Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding Daniels, DS, Kanugula, S, Tainer, JA, Mol, CD, Arvai, AS, Pegg, AE	EMBO J.	2000
14691244	Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase Rasimas, JJ, Pegg, AE, Ropson, IJ, Dalessio, PA, Fried, MG	Protein Sci.	2004
15964013	The structure of the human AGT protein bound to DNA and its implications for damage detection Rice, PA, He, C, Duguid, EM	J. Mol. Biol.	2005
22055184	DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation Xiong, LJ, Park, K, Mosammaparast, N, Dango, S, Shi, Y, Gygi, S, Sowa, ME, Harper, JW, Wu, F, Rubin, M	Mol. Cell	2011
12486230	Reversal of DNA alkylation damage by two human dioxygenases. Lindahl, T, Duncan, T, Bates, PA, Sedgwick, B, Trewick, SC, Koivisto, P	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