講義・セミナー
重点研究チーム「多細胞生物の構築原理と保障機構」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 : | 2015年12月 7日（月） 午後 5時～ 6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 : | Prof. Ciaran Morrison (National University of Ireland Galway, Ireland) |
| 演 題 : | Functions of the centrins in nucleotide excision repair and primary ciliogenesis |
講演要旨
Centrosomes, the principal microtubule-organising centres in animal cells, contain centrins, small, conserved calcium-binding proteins unique to eukaryotes. Centrin2 also binds to xeroderma pigmentosum group C protein (XPC), stabilising it, and its presence increases nucleotide excision repair (NER) activity in vitro. In previous work, we deleted all three centrin isoforms present in chicken DT40 cells and observed delayed repair of UV-induced DNA lesions, but no centrosome abnormalities. XPC recruitment to laser-induced UV-like lesions was only slightly slower in centrin-deficient cells than in controls, and levels of XPC and its partner HRAD23B were unaffected by centrin deficiency. We next tested the role of the centrin2 in the formation of primary cilia, antenna-like sensory microtubule structures that extend from basal bodies, plasma membrane-docked mother centrioles. Primary cilia arise in most cell types, but had not been described in lymphocytes. We found that efficient ciliogenesis in chicken DT40 B lymphocytes could be induced by serum starvation and required centrin2.
We then disrupted CETN2 in human retinal pigmented epithelial cells and despite having intact centrioles, they were unable to make cilia upon serum starvation, showing abnormal localisation of distal appendage proteins and failing to remove the ciliation inhibitor, CP110. Knockdown of CP110 rescued ciliation in CETN2-deficient cells. From these results, we concluded that centrin2 regulates primary ciliogenesis through controlling CP110 levels. CETN2 –deficient human cells are also deficient in NER and our current analyses are using mutagenesis to identify the specific activities of centrin2 that contribute to cilium formation and to DNA repair.