Study of calorie restriction using RNA-sequencing profiling in mismatch repair defected cells during chronological aging in Saccharomyces cerevisiae
Date Issued
2014
Date
2014
Author(s)
Teong, Xiao Tong
Abstract
Calorie restriction (CR) is able to reduce cancer progression and extend life span in various organisms. Age-related decline of DNA repair system such as mismatch repair (MMR) can reverse by CR. Defects in MMR have been linked to colorectal and sporadic cancers. Our previous results have demonstrated that CR can extend life span and maintain genome stability in MMR-defected cells during aging, but the mechanisms are poorly understood. Therefore, we suggest base excision repair (BER) which has been proven can be up-regulated by CR, is responsible to maintain genome stability in MMR-defected cells. However, we found that CR still able to extend life span and reduce mutations in MMR/BER -defected cells. And, CR has no effect on BER gene expression in MMR-defected cells during aging. To investigate the mechanisms responsible for CR to maintain genome stability in MMR-defected cells, the whole genome profile by performing RNA-seq has been analyzed. The most significant influenced genes which regulated by CR in MMR-defected cells are fatty acid metabolism, glyoxylate and dicarboxylate metabolism pathways. Besides, we demonstrate by using hydroxyurea to slow down cell cycle progression can maintain genome stability without CR in MMR-defected cells during aging, 50mM HU can reduce mutation by patching assay, however, HU also reduce life span in cells. Furthermore, we found that phosphorylation levels of H2A in CR cells are higher than non-CR cells. H2A phosphorylation is a marker of double strand break repair (DSBR). Further studies are needed to investigate whether CR would beneficial to MMR-defected cells through affecting cell cycle and DSBR pathway.
Subjects
calorie restriction
mismatch repair
cell cycle
aging
genome stability
SDGs
Type
thesis