Development of a methodology to map and quantify in the genome DNA single strand breaks.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21393
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Canela Andres 京都大学, 白眉センター, 特定准教授 (90837585)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: DNA一本鎖切断 / トポイソメラーゼI

Outline of Final Research Achievements

The main objective of this research is the development of a method to quantify and localize DNA single-strand breaks (SSBs) in the genome. SSBs are discontinuities in one strand of the DNA double helix. It is one of the most frequent damage in the DNA and its mainly produced by endogenous sources, although it can be also the consequence of exposure to UV, irradiation or to genotoxic agents. I have developed a method to quantify and localize DNA single-strand breaks (SSBs) in the genome. After checking the sensitivity detecting induced SSBs in vitro and in vivo I applied it to map the activity of Topoisomerase I in the genome, which creates a SSB as part of its catalytic cycle.

Free Research Field

DNA repair

Academic Significance and Societal Importance of the Research Achievements

DNAの一本鎖切断（SSB）は、DNAにおける最も一般的な損傷の一つである。一本鎖切断の蓄積は、癌、神経変性疾患、心不全などの病態に関与している。ゲノム中のSSBsの位置をマッピングする方法を開発することは、この種のDNA損傷の起源と修復、そしてそれらがどのように神経細胞の機能障害や早期老化につながるのか、また癌細胞におけるPARP阻害剤やトポイソメラーゼ阻害剤の作用機序の特徴をよりよく理解するのに役立つであろう。SSBがどのように認識され、修復されるかをよりよく理解することは、将来、がん治療のための改善された治療薬の設計に役立つ可能性がある。