Yeast molecular chaperone gene SSB2 is involved in the endoplasmic reticulum stress response.

The Saccharomyces cerevisiae chaperone gene SSB2 belongs to the Hsp70 family. Unlike other HSP70 genes, SSB2 gene expression is reduced after heat shock. It has been reported that Ssb2p can be cross-linked to ribosome-bound nascent polypeptide chains, suggesting a potential role of SSB2 in the endoplasmic reticulum (ER) stress response. In this study, SSB2-deletion and SSB2-overexpression yeast strains were generated and applied to explore the potential mechanism by which SSB2 is involved in the tunicamycin (TM)-induced ER stress response. We demonstrate for the first time that SSB2 deficiency results in reduced resistance to TM, while overexpression of SSB2 increases resistance to TM in an IRE1-HAC1 pathway-dependent manner; these observations are related to changes in intracellular unfolded protein response activities (under the TM-stressed condition). Additionally, SSB2 deletion induces early apoptosis and it may play a causal role in the shortened replicative life span of ssb2Δ mutants observed in this study. These findings highlight the involvement of SSB2 in ER stress responses and ageing in yeast.

CTT1 overexpression increases the replicative lifespan of MMS-sensitive Saccharomyces cerevisiae deficient in KSP1.

Ksplp is a nuclear-localized Ser/Thr kinase that is not essential for the vegetative growth of yeast. A global gene function analysis in yeast suggested that Ksplp was involved in the oxidative stress response; however, the underlying mechanism remains unclear. Here, we showed that KSP1-deficient yeast cells exhibit hypersensitivity to the DNA alkylating agent methyl methanesulphonate (MMS), and treatment of the KSP1-deficient strain with MMS could trigger abnormal mitochondrial membrane potential and up-regulate reactive oxygen species (ROS) production. In addition, the mRNA expression level of the catalase gene CTT1 (which encodes cytosolic catalase) and total catalase activity were strongly down-regulated in the KSP1-deleted strain compared with those in wild-type cells. Moreover, the KSP1 deficiency also leads to a shortened replicative lifespan, which could be restored by the increased expression of CTT1. On the other hand, KSP1-overexpressed (KSP1OX) yeast cells exhibited increased resistance towards MMS, an effect that was, at least in part, CTT1 independent. Collectively, these findings highlight the involvement of Ksplp in the DNA damage response and implicate Ksplp as a modulator of the replicative lifespan.

The MBD4 Glu346Lys polymorphism is associated with the risk of cervical cancer in a Chinese population.

OBJECTIVE: Methyl-CpG binding domain 4 (MBD4) protein functions as a DNA repair enzyme and plays an important role in maintaining genome integrity and carcinogenesis. The polymorphisms in the MBD4 gene may be associated with differences in DNA repair capacity and thereby influence an individual's susceptibility to cervical cancer. To verify this hypothesis, we examined the potential association between the MBD4 Glu346Lys polymorphism (rs140693, G>A) and the risk of cervical cancer in a Chinese population. METHODS: We genotyped the MBD4 Glu346Lys polymorphism in 146 cervical cancer cases and 320 healthy female subjects using polymerase chain reaction-based restriction fragment length polymorphism method. Unconditional logistic regression analysis was used to estimate the association between the genotypes and the risk of cervical cancer. RESULTS: We observed a significantly decreased risk of cervical cancer associated with the heterozygous Lys/Glu genotype (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.36-0.99; P = 0.046) and the homozygous Glu/Glu genotype (OR, 0.52; 95% CI, 0.30-0.89; P = 0.018), compared with the Lys/Lys homozygotes. Moreover, the reduced cervical cancer risk was more predominant among younger subjects or human papillomavirus-positive individuals carrying Glu/Glu genotypes (OR, 0.33; 95% CI, 0.14-0.78, P = 0.011; and OR, 0.27; 95% CI, 0.09-0.75, P = 0.013, respectively). CONCLUSIONS: The MBD4 codon 346 polymorphism may play a role in cervical cancer susceptibility in the Chinese population. Further larger case-control and functional studies are needed to validate these findings.

A single nucleotide polymorphism in EXO1 gene is associated with cervical cancer susceptibility in Chinese patients.

OBJECTIVE: The aim of this study was to investigate the association of Exonuclease1 (EXO1) genetic polymorphism and the development of cervical carcinoma. METHODS: This study was conducted with 126 patients diagnosed with cervical cancer and 278 people with no cancer history. The polymerase chain reaction-based restriction fragment length polymorphism was used to evaluate the K589E and C908G gene polymorphisms. Unconditional logistic regression analysis was used to estimate the association between the genotypes and the risk for cervical cancer. RESULTS: This is the first study on the role of EXO1 K589E (rs1047840) and EXO1 C908G (rs10802996) polymorphisms in cervical cancer in a Chinese population. Our results indicated that the EXO1 K589G polymorphism were significantly associated with the risk for cervical cancer. Compared with the G allele EXO1 K589E, the A allele increased the risk for cervical cancer (adjusted odds ratio, 1.67; 95% confidence interval, 1.13-2.45). By contrast, we have not found a significant association between the EXO1 C908G polymorphism and cervical cancer risk (P = 0.791). CONCLUSION: These findings indicate that the SNPs of EXO1 K589E may contribute to cervical cancer carcinogenesis in Chinese populations. A larger population study will need to be carried out to further validate the potential association of EXO1 genetic polymorphism and cervical carcinoma.