Novel molecular mechanism maintaining genomic homeostasis against environmental stresses

2014 Fiscal Year Final Research Report

• Project/Area Number: 24241019
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kobe University
• Principal Investigator: SUGASAWA Kaoru 神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 教授 (70202124)
• Co-Investigator(Kenkyū-buntansha): IWAI Shigenori 大阪大学, 基礎工学研究科, 教授 (10168544)
• Co-Investigator(Renkei-kenkyūsha): YOKOTA Hiroaki 光産業創成大学院大学, 光産業創成研究科, 准教授 (90415547) ; YOSHINO Ken-ichi 神戸大学, 自然科学系先端融合研究環バイオシグナル研究センター, 助教 (90280792)
• Research Collaborator: AKITA Masaki ; MATSUMOTO Syota ; TONE Daisuke ; ONISHI Yuki ; KINOSHITA Minoru
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 遺伝子 / ゲノム / 蛋白質 / DNA損傷修復 / 一分子解析

Outline of Final Research Achievements

This research project was aimed to understand the molecular bases, which enable the global genomic nucleotide excision repair (GG-NER) pathway to efficiently survey genomic DNA for damage caused by various environmental stresses. By using the defined cell-free GG-NER system reconstituted with purified recombinant protein factors, it was shown that certain endogenous DNA lesions, such as abasic sites, facilitate the damage recognition process in GG-NER, and that DNA repair efficiency is affected by the topological state of damaged DNA as well as protein phosphorylation. We also elucidated novel roles of ubiquitination and SUMOylation of the xeroderma pigmentosum group C (XPC) protein in recognition of ultraviolet (UV)-induced DNA photolesions mediated by the UV-damaged DNA binding protein complex. Finally, single molecule imaging experiments revealed one-dimensional diffusion of the XPC protein during the search for lesions along DNA.

Free Research Field

生化学・分子生物学