2019 Fiscal Year Final Research Report
Elucidation of the homology search mechanism and its regulation occurring in a chromatin environment during homologous recombination
| Project/Area Number |
17H01408
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Genome biology
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| Research Institution | The University of Tokyo (2018-2019)
Waseda University (2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
清水 光弘 明星大学, 理工学部, 教授 (80231364)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | ゲノム維持修復 / ゲノム多様性 / ゲノム進化・再編 / 遺伝情報複製・再編 / ゲノム機能 / 活性発現の分子機構 / 染色体構築・機能・分配 / 生体高分子構造・機能 |
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| Outline of Final Research Achievements |
The purpose of this study is to clarify how "DNA homology search", a key reaction step of homologous recombination, takes place on the chromatin structure. Homologous recombination is essential for the maintenance and reorganization of genomic DNA. However, its mechanism has been elusive. By combining chromatin reconstitution technology, in vitro recombination assays, and structural biological analysis by X-ray crystallography and cryo-electron microscopy, we studied the mechanisms underlying DNA homology search taking place on the chromatin. We have elucidated (1) the biochemical properties of SYCP3, a factor that plays a role in meiotic recombination, (2) the fundamental structure of the highly condensed heterochromatin, and (3) the complex structures of RAD52 and DNA that provide important insights into the mechanisms of DNA homology search.
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| Free Research Field |
生化学、構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
DNAの二重鎖切断損傷は、ゲノム情報に重篤なダメージを与える。それゆえ、その正確な修復は生物の生存に必須の機構であり、相同組換えはその中心的な役割を果たす。相同組換えは、原核生物から真核生物に至るまで生物界に保存されている重要な生命維持機構である。また減数分裂期において、雌雄由来のゲノムDNA情報を交換する遺伝的組換えにおいても機能し、生物の多様性を生む機構をも担っている。二重鎖切断損傷修復の破綻が、がんなどの重篤な疾病の原因になっていることも報告されており、そのメカニズムの理解は、学術的および社会的に大きな意義を持つ。
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