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The effect of calorie restriction on the genome stability in DNA repair defective cells
Author(s) -
Lo Yi-Chen,
Leow Siew Keng,
Wu Pei-Shang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb89
Subject(s) - msh2 , msh6 , dna mismatch repair , dna repair , mutant , biology , mutation , werner syndrome , genome instability , genetics , saccharomyces cerevisiae , dna damage , dna , microbiology and biotechnology , mlh1 , phenotype , gene , helicase , rna
It has been found that calorie restriction (CR) can extend the average and maximum life span from yeast to primates and delay the onset of age‐associated pathologies. Mismatch repair and double strand break repair systems are major DNA repair pathways whose function are critical for maintaining genome stability. The inactivation of these systems in human pathway has been reported to cause cancer predisposition such as Hereditary Nonpolyposis Colorectal Cancer, Werner and Bloom syndromes. By using Saccharomyces cerevisiae model system for CR and aging studies, DNA repair defective cells ( msh2Δ , msh3Δ , msh6Δ and sgs1Δ ) were cultured with normal (2% glucose) and CR (0.5% glucose) medium. Genome stability studies were analyzed by CAN r , Hom r and Lys r mutation assay. Results show that CR can significantly extend the lifespan of all wild‐type and mutants. Besides, CR shows significant decrease in HOM r mutation frequency by 2.7 × 10 4 ‐fold in msh2Δ mutant, whereas by 2.4 × 10 6 ‐fold and 1.4 × 10 6 ‐fold reduction in msh3Δ mutant for HOM r and LYS r assay respectively. In addition, for sgs1Δ mutant, there are significant decreases in HOM r and LYS r assay by two‐fold. Under normal condition, msh2Δ , msh3Δ and sgs1Δ cells found to have regrow phenotype upon aging. However, this phenotype was diminished under CR condition. Thus, CR promotes genome stability in DNA repair defective cells especially in msh2Δ , msh3Δ and sgs1Δ mutants.