In vitro approach of inflammatory carcinogenesis by the elucidation of cellular response to opposing DNA damages.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17055
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Moriwaki Takahito 川崎医科大学, 医学部, 助教 (60734100)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: DNA損傷 / 突然変異 / がん / 炎症

Outline of Final Research Achievements

In this study, we investigated how opposing DNA damage is recognized and repaired in cells to elucidate the mechanism of inflammatory carcinogenesis. A search for enzymes with binding activity to opposing DNA damage yielded a band indicating the presence of a protein that binds specifically to it. Glycosylase activity was confirmed and showed that uracil was actively removed from opposing DNA damage, but no activity for removal of 8-oxoguanine was observed; observation of AP lyase activity by Trapping assay showed that removal of uracil in opposing DNA damage was not dependent on UNG or UDG, suggesting that the removal of uracil in opposing DNA damage is carried out by mono-functional glycosylases such as UNG and UDG. Taken together, these results indicate that cells have specific repair mechanisms for opposing DNA damage.

Free Research Field

DNA損傷

Academic Significance and Societal Importance of the Research Achievements

本研究によりヒトに対向型DNA損傷を認識するタンパク質が存在することが明らかとなり、またその機能の一端が分かった。対向型DNA損傷は炎症性発がんと密接に関連していると予測されるため、このタンパク質を同定し、その機能を明らかにすることは炎症性発がんの理解につながる。全がんの15%は何らかのウイルス感染とそれに伴う炎症が原因であると見積もられている。それゆえ炎症性発がんの理解はがんの罹患リスクそのものの低下に大きく寄与すると期待される。