• BMB Reports
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• v.42 no.1
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• pp.53-58
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• 2009

The methyl-directed mismatch repair (MMR) mechanism has been extensively studied in vitro and in vivo, but one of the difficulties in determining the biological relationships between the MMR-related proteins is the tendency of MutL to self-aggregate. The properties of a stable MutL homologue were investigated using a thermostable MutL (TmL) from Thermotoga maritima MSB8 and whose size exclusion chromatographic and crosslinking analyses were compatible with a dimeric form of TmL. TmL underwent conformational changes in the presence of nucleotides and single-stranded DNA (ssDNA) with ATP binding not requiring ssDNA binding activity of TmL, while ADPnP-stimulated TmL showed a high ssDNA binding affinity. Finally, TmL interacted with the T. maritima MutS (TmS), increasing the affinity of TmS to mismatched DNA base pairs and suggesting that the role of TmL in the formation of a mismatched DNA-TmS complex may be a pivotal observation for the study of the initial MMR system.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1214-1220
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• 2005

Decreased porin-mediated outer membrane penetration of hydrophilic antibiotics is a common mechanism of antibiotic resistance in Gram-negative bacteria. This study was undertaken to determine whether a null mutation in Pseudomonas putida would suppress porin synthesis, and therefore reduce the susceptibility of the organism to streptomycin, norfloxacin, and tetracycline. Inverse PCR amplification and double-stranded DNA sequencing were used to identify chromosomal genes carrying TnphoA'-1 inserts. Genome database available was used to identify putative homologue genes, one of which encodes protein with homology to domains of the MutS of P. putida, suggesting a crucial role in the multidrug resistance. Increased resistance to streptomycin, norfloxacin, and tetracycline might be due to accumulation of compensatory mutations. Either no growth or slow growth was observed in P. putida KH1027 when grown in minimal medium containing gluconate, glucose, or citrate; however, it is not clear whether the growth patterns contributed to the multidrug resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6411-6413
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• 2013

Adenocarcinoma of esophagus (AE) is a complex disease, affected by a variety of genetic and environmental factors. Much evidence has shown that the MutY glycosylase homologue (MUTYH) plays a key role in the pathogenesis of many cancers. However, there have been no reports on influence on AE in the Han Chinese population. The objective of this study was to investigate this issue. A gene-based association study was conducted using three single nucleotide polymorphisms(SNPs) reported in previous studies. The three SNPs (rs3219463, rs3219472, rs3219489) were genotyped in 207 unrelated AE patients and 249 healthy controls in a case-control study using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results revealed that the genotype distribution of rs3219472 differed between the case and control groups (OR=1.66,95%CI=1.11-2.48, P=0.012), indicating that an association may exist between MUTYH and AE. These findings support a signifcant role for MUTYH in AE pathogenesis in the Han Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6403-6409
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• 2013

Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic $G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 $G{\rightarrow}A$, exon 1-292 $G{\rightarrow}A$ and intron 1+11 $C{\rightarrow}T$, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 $A{\rightarrow}G$, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 $C{\rightarrow}T$, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 $T{\rightarrow}A$), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 $A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2 $A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.