Analysis of DNA-damage-tolerance mechanisms that facilitate restart of stalled DNA replication

2016 Fiscal Year Final Research Report

• Project/Area Number: 25340030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyoto University
• Principal Investigator: MOTEGI AKIRA 京都大学, 医学研究科, 助教 (80452332)
• Co-Investigator(Renkei-kenkyūsha): MASUTANI MITSUKO 長崎大学, 大学院医歯薬総合研究科, 教授 (60238904)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: DNA損傷トレランス / 複製後修復 / 組換え修復 / ユビキチン

Outline of Final Research Achievements

In this study, we showed that simultaneous genetic disruption of the ubiquitin ligase SHPRH and FANC, one of core factors in the Fanconi Anemia (FA) pathway, substantially rescued hypersensitivity towards cisplatin, an inter-strand cross-linking (ICL) agent. This observation suggests that SHPRH-dependent pathway antagonizes to the FA pathway. We also showed that PARP-1 prohibits resection in in vitro extract assay and that low expression of CtIP nuclease in breast cancer correlates with poor prognosis and hypersensitivity towards PARP inhibitors.

Free Research Field

分子生物学