2019 Fiscal Year Final Research Report
Development of a novel cancer radiotherapy based on the regulatory network for the DNA damage response
Project/Area Number |
17K10471
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Radiation science
|
Research Institution | The University of Tokyo |
Principal Investigator |
Hosoya Noriko 東京大学, 大学院医学系研究科(医学部), 准教授 (00396748)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Keywords | DNA損傷応答 / がん / 細胞核内微小環境 / 放射線抵抗性 |
Outline of Final Research Achievements |
SYCE2 is one of the components of the synaptonemal complex, which is formed between homologous chromosomes to ensure their connection in meiosis. This protein is not expressed in normal mitotic cells but is aberrantly expressed at varying levels in somatic cancer cells, suggesting that it is a cancer-testis antigen. In this study, we investigated the mitotic roles of SYCE2. We found that SYCE2 insulates heterochromatin protein 1α from heterochromatin and promotes ATM-dependent DNA double-strand break repair and radioresistance. This finding suggests that SYCE2 plays a role in the link between the nuclear microenvironment and the DNA damage response in somatic cells.
|
Free Research Field |
放射線基礎医学、放射線生物学、腫瘍生物学
|
Academic Significance and Societal Importance of the Research Achievements |
SYCE2が細胞核内においてクロマチン制御分子HP1αをヘテロクロマチン領域から引き離すことにより、がん細胞におけるDNA修復能を増強することが明らかになり、これまで生殖における役割しか知られてこなかったSYCE2の体細胞における役割を初めて示すことができた。SYCE2はその発現レベルに応じてがん細胞のDNA修復能を規定すると考えられるため、SYCE2を発現するがんのDNA修復能力の特性に基づいた新しい治療の構築に応用できることが期待される。
|