A novel DNA damage recognition protein in Schizosaccharomyces pombe.
A novel DNA damage recognition protein in Schizosaccharomyces pombe.
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粟酒裂殖酵母中一种新型 DNA 损伤识别蛋白。
DOI：
10.1093/nar/gkl270
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发表时间：
2006
影响因子：
14.9
通讯作者：
Margison GP
中科院分区：
文献类型：
--
作者：
Pearson SJ;Wharton S;Watson AJ;Begum G;Butt A;Glynn N;Williams DM;Shibata T;Santibáñez-Koref MF;Margison GP
Toxic and mutagenic O6-alkylguanine adducts in DNA are repaired by O6-alkylguanine-DNA alkyltransferases (MGMT) by transfer of the alkyl group to a cysteine residue in the active site. Comparisons in silico of prokaryotes and lower eukaryotes reveal the presence of a group of proteins [alkyltransferase-like (ATL) proteins] showing amino acid sequence similarity to MGMT, but where the cysteine at the putative active site is replaced by tryptophan. To examine whether ATL proteins play a role in the biological effects of alkylating agents, we inactivated the gene, referred to as atl1+, in Schizosaccharomyces pombe, an organism that does not possess a functional MGMT homologue. The mutants are substantially more susceptible to the toxic effects of the methylating agents, N-methyl-N-nitrosourea, N-methyl-N′nitro-N-nitrosoguanidine and methyl methanesulfonate and longer chain alkylating agents including N-ethyl-N-nitrosourea, ethyl methanesulfonate, N-propyl-N-nitrosourea and N-butyl-N-nitrosourea. Purified Atl1 protein does not transfer methyl groups from O6-methylguanine in [3H]-methylated DNA but reversibly inhibits methyl transfer by human MGMT. Atl1 binds to short single-stranded oligonucleotides containing O6-methyl, -benzyl, -4-bromothenyl or -hydroxyethyl-guanine but does not remove the alkyl group or base and does not cleave the oligonucleotide in the region of the lesion. This suggests that Atl1 acts by binding to O6-alkylguanine lesions and signalling them for processing by other DNA repair pathways. This is the first report describing an activity that protects S.pombe against the toxic effects of O6-alkylguanine adducts and the biological function of a family of proteins that is widely found in prokaryotes and lower eukaryotes.
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通过大肠杆菌的烷基转移酶样蛋白抑制O6-甲基鸟嘌呤-DNA甲基转移酶。
影响因子：
14.9
作者：
Pearson, SJ;Ferguson, J;Santibanez-Koref, M;Margison, GP
通讯作者：
Margison, GP
DOI：
10.1073/pnas.82.9.2688
发表时间：
1985-01-01
影响因子：
11.1
作者：
DEMPLE, B;SEDGWICK, B;LINDAHL, T
通讯作者：
LINDAHL, T
DOI：
10.1016/0027-5107(90)90173-2
发表时间：
1990-07-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
BERANEK, DT
通讯作者：
BERANEK, DT
DOI：
10.1073/pnas.87.2.686
发表时间：
1990-01-01
影响因子：
11.1
作者：
TANO, K;SHIOTA, S;MITRA, S
通讯作者：
MITRA, S
影响因子：
64.8
作者：
Friedberg, EC
通讯作者：
Friedberg, EC