Analysis of the contribution of transcription to homologous recombination pathway

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11648
• 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: Kanazawa Medical University
• Principal Investigator: SAKASAI Ryo 金沢医科大学, 医学部, 講師 (10549950)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: DNA二本鎖切断 / 組換え修復 / 非相同末端連結 / 転写

Outline of Final Research Achievements

Two major pathways are known to repair DNA double-strand breaks (DSBs): the homologous recombination pathway (HR) and the non-homologous end joining pathway (NHEJ). Although the selection mechanism of the repair pathways is still unclear, we considered that the exposure of single-stranded DNA at the end of a DNA break (DNA end resection) is an important step toward the HR pathway, and that transcription or transcripts may promote resection. Analysis using transcription inhibitors showed that the accumulation of HR-related proteins in DSB sites was suppressed, suggesting that transcription is one of the regulatory factors of the HR pathway. In addition, the localization of 53BP1, an anti-resection factor, was also affected, suggesting that transcription is not only involved in promoting HR, but may also be widely involved in the DNA damage response.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

我々の細胞に含まれるDNAが放射線や抗がん剤によって切断されると強い毒性を引き起こすが、細胞はDNAを修復する機能を持つ。DNA切断の修復には「連結」と「組換え」の経路が知られているが、その使い分けについては不明である。DNA切断修復は、がん治療における放射線や抗がん剤の有効性や、将来の医学応用が期待されるゲノム編集機構と密接に関係しており、その理解が重要であると考えられる。研究代表者らは、転写が組換え経路を促進する可能性を考えて解析したところ、組換え関連因子のDNA切断への集積が抑えられた。また、組換えの抑制因子にも影響が認められ、転写がDNA損傷応答に広く関与している可能性が考えられる。