Molecular characterization of cell fate determination in the DNA damage response

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Nagoya City University
• Principal Investigator: JOHMURA Yoshikazu 名古屋市立大学, 医学(系)研究科(研究院), 助教 (40616322)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 老化 / がん / DNA損傷 / 細胞周期

Outline of Final Research Achievements

DNA damage response is known to induce senescence as well as transient cell cycle arrest and apoptosis, but molecular mechanisms of how cells determine　whether or not to undergo senescence are largely unknown. This study show　that suppression of DNA repair pathways extends the duration of Chk1-dependent G2 checkpoint activation and sensitizes cells tosenescence through enhancement of mitosis skipping. Extension of G2 checkpoint activation by introduction of the TopBP1 activation domain sensitizes cells to senescence. Importantly, fibroblasts from progeroid syndromes tested shows a strong correlation between　a drastic extension of G2 checkpoint activation and an increase in the susceptibility to senescence, suggesting that extension of G2 checkpoint activation caused by defective DNA repair is critical for senescence
predisposition in progeroid syndrome patients. These results indicate that the duration of Chk1-dependent G2 checkpoint directs cells to senescence.

Free Research Field

分子細胞生物学