Functional analysis of cellular tolerance to chronic genotoxic stress in Saccharomyces cerevisiae

2015 Fiscal Year Final Research Report

• Project/Area Number: 23247002
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Genetics/Genome dynamics
• Research Institution: Gakushuin University
• Principal Investigator: Hishida Takashi 学習院大学, 理学部, 教授 (60335388)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: DNA損傷 / 出芽酵母 / DNA損傷トレランス

Outline of Final Research Achievements

DNA damage tolerance (DDT) provides a mechanism to tolerate chronic genotoxic stress during replication, allowing the lesions to be repaired after replication, thus reducing the overall risk of genome instability. The post-translational modification of PCNA, proliferating cell nuclear antigen, by ubiquitination plays an important role in coordinating the process of DNA damage tolerance. Here we examined the effects of mutations in the Mgs1 ATPase, UBZ and C-terminal domains on DNA damage tolerance. The results demonstrate that the UBZ domain negatively regulates the DDT pathway, whereas the C-terminal domain stimulates the homologous recombination pathway, implicating a role for Mgs1 in the regulation of both pathways. We also found an increasing number of metabolic compounds, such as trehalose and reactive oxygen species, linked with the maintenance of genome integrity. These observations underscore the importance of metabolic functions on replication stress tolerance.

Free Research Field

分子遺伝学