講義・セミナー
重点研究チーム「蛋白質のシグナル伝達機能研究」学術講演会のお知らせ
以下のセミナーを開催いたします。
| 日 時 : | 2010年11月 1日（月） 午後 4時～ 5時30分 |
| 場 所 : | 神戸大学・遺伝子実験センター・5階研修室 |
| 講 師 : | Dr. Nicolas H. Thomä (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland) |
| 演 題 : | Structural basis of UV-damage recognition by the DDB1-DDB2-Cul4 complex |
講演要旨
The DDB1-DDB2-Cul4 complex serves in the recognition of UV-induced DNA damages such as 6-4 photoproducts (6-4PP) and cyclobutane pyrimidine dimers (CPD). In the global genome branch of nucleotide excision repair (NER), DDB1-DDB2-Cul4 arrives first at the lesion. It targets nucleosomes for ubiquitination, and facilitates and regulates the coordinated arrival and departure of repair proteins at the site of damage. (i) We will present how the DDB1-DDB2 complex recognizes CPD lesions, a type of DNA damage that due to its relatively small duplex distortion escapes detection by other damage binding factors. (ii) We additionally present the structure of the entire 310kDa DDB1-DDB2-Cul4 ubiquitin ligase complex in its DNA bound form. Based on structural data we could demonstrate that the Cul4 ligase is attached to DDB1 in a mobile fashion able to target substrates within defined geometric constraints around the site of damage. (iii) Unlike all other tested DNA damage detection proteins in NER, we show that this ligase is able to directly interrogate mono-nucleosomes for the presence of DNA damage. A molecular and structural model for damage recognition on nucleosomal targets will be presented. Our work demonstrates how the DDB1-DDB2-Cul4 ligase complex has adapted to deal with nucleosome embedded DNA damages, and establishes a common molecular architecture within the family of Cul4-DDB1 ligases