Study of genomic instability risk arisen by UV and ionizing radiation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Yoshioka Ken-ichi 国立研究開発法人国立がん研究センター, 研究所, ユニット長 (70321916)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ゲノム不安定性 / 放射線 / 紫外線 / DNA損傷

Outline of Final Research Achievements

Ultra Violet (UV) light, primarily inducing cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PPs), risks skin cancer with genomic instability. However, it is still unclear how the photoproducts are associated with genomic instability. Similarly, ionizing radiation could also cause multiple types of DNA damages, it is not clear which of those are responsible. Here we studied that replication stress-associated DNA double strand breaks (DSBs) risking genomic instability are those mechanistic backgrounds. We observed that both UV and ionizing radiation are associated with DNA replication stress and hence risking genomic instability. Resulting cells are subjected to the clonal evolution of cells mutated in the ARF/p53 pathway.

Free Research Field

DNA修復

Academic Significance and Societal Importance of the Research Achievements

放射線や紫外線のばく露は、ゲノム不安定性を伴うがんのリスク要因となることが知られている。しかし、これらの外的ストレスによって生じた様々なタイプのDNA損傷のなかで、どのタイプの損傷が、どの様にゲノム不安定性の誘導に関わるのかは不明であった。本研究からは、放射線および紫外線で生じるDNA損傷とゲノム不安定性誘導の関係、特に、その作用点が明確になってきた。