DNA-protein cross-links and chromatin remodeling

2014 Fiscal Year Final Research Report

• Project Area: Coupling of replication, repair and transcription, and their common mechanism of chromatin remodeling
• Project/Area Number: 22131010
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hiroshima University
• Principal Investigator: IDE HIROSI 広島大学, 理学(系)研究科(研究院), 教授 (30223126)
• Co-Investigator(Renkei-kenkyūsha): NAKANO Toshiaki 広島大学, 大学院理学研究科, 助教 (10526122)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: ゲノム損傷 / DNA複製 / 転写 / DNA修復

Outline of Final Research Achievements

In this study, we have assessed the biological effects and repair mechanism of DNA-protein cross-link (DPC) damage. DPCs inhibited the translocation of replicative helicases, showing a unique mechanism of replisome stalling. DPCs caused backup of RNA polymerases, resulting in error-prone transcription. We have established a novel method of DPC detection using fluorescence labeling, and analyzed the induction of genomic DPCs by aldehydes, ionizing radiation, and anticancer drugs and their repair. We also showed that knockdown of RUVBL2, an essential subunit of a chromatin remodeling complex INO80, conferred a moderate sensitivity to DPC-inducing agents, suggesting a role of the chromatin remodeling complex in homologous recombination.

Free Research Field

DNA損傷の生物影響と修復