Analysis of Translesion synthesis (TLS) mechanism by novel assay method

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K12598
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Tokyo Metropolitan University
• Principal Investigator: Hirota Kouji 首都大学東京, 理工学研究科, 教授 (00342840)
• Research Collaborator: Julian Sale ケンブリッジ大, 教授 ; Doherty Aidan サセックス大, 教授 ; Branzei Dana IFOM研究所, 教授 ; Scott Keeney スローンケタリング癌研究所, 教授 ; Hoffman Charles S. ボストン大, 教授 ; Pommier Yves NIH, 教授
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: DNA損傷 / 損傷乗り越え / TLSポリメラーゼ / 変異

Outline of Final Research Achievements

Translesion DNA synthesis (TLS) is pivotal for releasing replication arrest at DNA damage on the template strand. TLS polymerases are involved in this bypass replication across damaged template. However, the mechanism to select a polymerase to carry out TLS across some specific damage has not been elucidated. For the bypass of UV induced T-T dimer damage, Polymerase-η can replicate in error free manner, while other TLS polymerases induce replication erorrs during TLS and thereby induce mutations. In this study, we employed novel TLS assay using artifical damaged oligo DNAs and revealed selectivity of TLS polymerase to the kind of DNA damage.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

これまで不明であった損傷乗り越え機構において機能するTLSポリメラーゼ群の包括的多重変異細胞を作成し、これらポリメラーゼ酵素群の関係性を明らかにすることができた。この機構は、発癌につながるDNA変異に関わるため、癌発生のメカに住むにつながるとともに、新規のがん治療法開発につながる知見であり社会的意義は大きい。