Elucidation of novel mechanism to lead DNA over-replication

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06271
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: The University of Tokushima
• Principal Investigator: TSUNEMATSU Takaaki 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70726752)
• Research Collaborator: ISHIMARU Naozumi ; KUDO Yasusei ; ARAKAKI Rieko ; KAWAI Hidehiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: DNA複製 / ユビキチン / タンパク分解

Outline of Final Research Achievements

DNA replication is restricted to occur once per cell cycle and its deregulation cause excessive chromosomal numbers called DNA re-replication. The chromosomal abnormality is one of the hallmarks of cancer. So, the understanding of its regulation is important for analyzing cancer biology. In this study, we try to identify novel mechanisms which suppress DNA re-replication by using genome-wide siRNA library. We found that knockdown of each genes did not cause DNA re-replication besides known regulators. Finally, we identified the novel regulators of DNA re-replication by siRNA screening with DNA re-replication inducing reagent.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

本研究で着目するDNA再複製と呼ばれる現象は染色体数の異常な増加を引き起こすことから発癌や癌の進展に関与する可能性があり、癌の生物学を理解する上で重要な生命現象と考えられる。一方で癌細胞に持続的にDNA再複製を誘導すると細胞老化を引き起こし、細胞死に至ることから、癌の治療法としても可能性を有しており、その制御機構の解明は非常に意義深いと考えられる。本研究成果によって同定した新規のDNA再複製制御機構が発癌及び癌の進展の理解、癌の治療法の開発の新たな分子基盤となりうると考える。