Disease relevance of METHYL METHANESULFONATE

• Here, we report that reactivation of methylmethanesulfonate (MMS)-treated single-stranded DNA phages, M13, f1, and G4, was decreased dramatically in alkB mutants [1].
• We cloned the MpgII genes from T. maritima and from Aquifex aeolicus and found that both genes could restore methylmethanesulfonate (MMS) resistance to Escherichia coli alkA tagA double mutants, which are deficient in the repair of alkylated bases [2].
• Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone [3].
• Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate [3].
• Methylmethanesulfonate-induced DNA damage and its repair in cultured human fibroblasts: normal rates of induction and removal of alkali-labile sites in xeroderma pigmentosum (group A) cells [4].

Psychiatry related information on METHYL METHANESULFONATE

• We have shown that fibroblasts, lymphocytes and lymphoblasts from patients with Alzheimer's disease (AD) are deficient in the repair of DNA damage induced by the alkylating agents methylmethane sulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [5].

High impact information on METHYL METHANESULFONATE

• Both subunits are required in vivo for resistance to DNA damage by methylmethane sulfonate (MMS) [6].
• Consistent with this theory, stationary phase alkB cells were less MMS sensitive than rapidly growing cells [1].
• The single-strand damage processed by AlkB was primarily cytotoxic and not mutagenic and was induced by SN2 methylating agents, MMS, DMS, and MeI but not by SN1 agent N-methyl-N-nitrosourea or by gamma irradiation [1].
• Increased sensitivity to genotoxic agents, particularly ultraviolet light and methylmethanesulfonate, shows that Brca2 function is essential for the ability to survive DNA damage [7].
• 53BP1 foci formation is not restricted to gamma-radiation but is also detected in response to UV radiation as well as hydroxyurea, camptothecin, etoposide, and methylmethanesulfonate treatment [8].

Chemical compound and disease context of METHYL METHANESULFONATE

• Escherichia coli lon mutants lack a major ATP-dependent protease, are sensitive to UV light and methylmethane sulfonate (MMS), and overproduce capsular polysaccharide [9].

Biological context of METHYL METHANESULFONATE

• Expression of wild-type, but not kinase-inactive, Lyn weakened promotion of apoptosis by GADD34 following treatment with methyl-methanesulfonate or ionizing radiation in HEK293 and HeLa cells [10].
• Of the 10 mutants that have been shown to contain DNA sequence alterations, 2 exhibit a split phenotype with respect to complementation of the growth defect and methylmethanesulfonate sensitivity of the double mutant; one is a null mutant [11].
• In yng2, MMS treatment causes a persistent Mec1-dependent intra-S-phase checkpoint delay characterized by slow DNA repair [12].
• DNA polymerase beta (Pol beta) transfection was ineffective in conferring resistance to methylmethane sulfonate (MMS) [13].
• However, cell cycle analysis and protease assay studies strongly suggest that methylmethanesulfonate may activate a cellular protease to degrade DNMT1 [14].

Anatomical context of METHYL METHANESULFONATE

• These cell lines were significantly more resistant to the cytotoxic effects of methylmethanesulfonate and N-methyl-N-nitrosourea than their parent cell lines, indicating that 3-methyladenine repair is a limiting factor in cellular resistance to these methylating agents [15].
• Fibroblasts from the patient with Turcot's syndrome were hypersensitive to MMS, having a D0 value of 0.24 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 value of 0.95 mM (p less than 0.01) compared with the normal average value of 1.3 mM [16].
• We found that CHO cells with high expression of IGFII have a shortened cycling time and a diminished G1 checkpoint after treatment with methylmethane sulfonate (MMS), a DNA base-damaging agent, when compared with CHO cells with very low IGFII expression [17].
• PCA-1-transfected COS-7 cells further showed resistance against MMS-induced cell death [18].
• In this study, NIH 3T3 cells were exposed to methylmethanesulfonate (MMS), revealing that the agent clearly induced c-jun expression with a peak at 2 h [19].

Associations of METHYL METHANESULFONATE with other chemical compounds

• Furthermore, the mutation frequency induced by methylmethanesulfonate was reduced to 50% of normal by expression of 3-methyladenine I activity in the Chinese hamster cells, indicating that m3A is not only a cytotoxic but also a premutagenic lesion in mammalian cells [15].
• Mobility-shift and structural analyses show that the MBD of MBD1 binds a methyl-CpG pair (mCpG x mCpG) but not the methyl-CpG pair containing a single 7-methylguanine (N) (mCpG x mCpN) that is known as one of the major lesions caused by MMS [20].
• The frequency of mutations formed in the hypoxanthine phosphoribosyl transferase (hprt) locus was investigated after methylmethanesulfonate (MMS), ethylmethanesulfonate (EMS), N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) exposure [21].
• This review focuses on the DNA methyl damage caused by MMS and MNNG for each site of potential methylation to summarize what is known about the repair of such damage and the downstream responses and consequences if the damage is not repaired [22].
• The protein kinase inhibitor staurosporine and the temperature sensitive (ts) p34cdc2 mutant reduced induction by the alkylating agent methylmethane sulfonate (MMS) of the rodent gadd45 and gadd153 genes [23].

Gene context of METHYL METHANESULFONATE

• We further demonstrate that knockdown of MBD1 by specific small interfering RNAs significantly increases cell sensitivity to MMS [20].
• A comet assay demonstrated that DNA repair after MMS or UV treatment was impaired in the cells expressing nuclease-deficient FEN-1 but not in the cells with double-mutated FEN-1 [24].
• Other aspects of the genomic responses were independent of Mec1p, and likely independent of DNA damage, suggesting the pleiotropic effects of MMS and ionizing radiation [25].
• Transcription factors NF-YA regulate the induction of human OGG1 following DNA-alkylating agent methylmethane sulfonate (MMS) treatment [26].
• Deleting the APN1 gene largely restored the resistance of rad27 mutants to MMS [27].

Analytical, diagnostic and therapeutic context of METHYL METHANESULFONATE

• By Northern blotting analysis, the increased expression of IL1 alpha, IL1 beta, and IL6 genes was shown to occur at 30 min of Mit C and MMS treatment and to decline after 8 h [28].
• Hcr- Mut+ (non-mutator) and Hcr+ Mut-. In this work complementation tests were done by examining UV- and MMS-sensitivity and host cell reactivation in heterogenotes containing combinations of uvrD3, uvrE156, recL152, and the MMS-resistant mutations derived from uvrD3 [29].
• The in vitro formation of adducts from human haemoglobin formed by alkylation with methyl-methanesulphonate, dimethyl sulphate and iodoacetamide was determined with isoelectric focusing in ultra-thin polyacrylamide gels with a non-linear pH gradient [30].
• Agarose gel electrophoresis of genomic DNA isolated from wild-type and chl1 cells, after recovery from MMS treatment, suggested that the wild-type was more proficient in the repair of DNA damage than the mutant [31].

References