Rich Tan

Cancer cells, like yeast, use fermentation despite the presence of oxygen, a phenomenon called aerobic glycolysis. The advantage is that it maintains many C-C bonds of glucose, allowing highly proliferating cells to produce the biomolecules that are necessary for cytokinesis. However, aerobic glycolysis is less energy-efficient than respiration, and it must operate at high frequency and produces large amounts of lactate, which modifies and stimulates DNA repair enzymes via lysine lactylation. This makes cancer cells resistant to radiotherapy, which requires a combination with chemotherapy using drugs that inhibit DNA repair. However, this converts healthy cells to cancer cells, indicating that research is still required regarding the relationship between glycolysis and cancer. Using yeast as a model, we discovered that the glycolytic enzymes TPI and GAPDH (Tpi1p and Tdh1-3p in yeast) interact with the DNA damage-dependent Checkpoint Rad9p (53BP1/BRCA1/MDC1 in humans). We propose that Tpi1p and Tdh1-3p override Rad9p, allowing cells with damaged DNA to proliferate. We isolated tpi and gapdh mutant strains that are deficient in DNA repair. While the tpi mutant strain has lower enzymatic activity, the gapdh mutant strains have normal enzymatic activity, confirming previous reports that GAPDH moonlights in the DNA damage response.

Cancer cells, like yeast, use fermentation despite the presence of oxygen, a phenomenon called aerobic glycolysis. The advantage is that it maintains most of the C-C bonds of glucose, allowing highly proliferating cells to produce the biomolecules that are necessary for cytokinesis. However, aerobic glycolysis is less energy-efficient than respiration, and it must operate at a higher frequency and produces more toxic by-products like methylglyoxal, which damages DNA. Cancer cells, like yeast cells, developed efficient systems to repair their damaged DNA. This makes cancer cells resistant to radiotherapy, which requires a combination with chemotherapy using drugs that inhibit DNA repair. However, this converts healthy cells to cancer cells, indicating that more research is required regarding the relationship between glycolysis and cancer. Using yeast as a model, we have discovered that the glycolytic enzymes TPI1 and GAPDH interact with the DNA damage-dependent checkpoint Rad9p. Furthermore, we have isolated TPI1 and GAPDH mutant strains that are unable to repair their damaged DNA. The TPI1 mutant strain has lower TPI enzymatic activity, suggesting that it accumulates methylglyoxal, while the GAPDH mutant strains have normal GAPDH enzymatic activity, confirming that GAPDH moonlights in the DNA Damage Response.

Gambling Disorder (GD) is a highly stigmatised condition with serious psychological, social and financial consequences. Limited public recognition regarding GD may hinder help-seeking, shape beliefs about recovery and reinforce stigma. This study seeks to establish the extent of recognition of GD as well as stigma towards it in Singapore’s population using a vignette-based approach. Data from 595 participants from a nationwide vignette-based study on mental health literacy were analysed using weighted analysis and multivariable logistic and linear regression to address the aims. Participants received a vignette on GD and answered questions related to recognition of the condition, sociodemographic information, perception of help-seeking and chances of recovery for GD. Furthermore, the study also assessed stigma across three domains: “weak not sick”, “dangerous/unpredictable”, and “social distancing”. The majority of participants (75.63%) correctly identified the vignette as GD. Informal networks, non-medical professional support and community-based resources were highly recommended help-seeking sources. Majority of the respondents believed that individuals with GD who seek appropriate help can achieve full recovery while those who do not would experience worsening of the condition. Predictors of higher stigma towards GD included older age, female gender, Malay or Indian ethnicity, being married, having friends or family members with similar problem and a high monthly income. While recognition of GD was relatively high among respondents, stigma toward individuals with GD remains prevalent particularly among certain demographic groups. Data from this study can help to improve public health interventions and policy efforts to better support those with GD.