|開催日時：||2018年7月4日 17:00 ～ 18:00|
|所属：||Professor and Head of Laboratory, The Rockefeller University, Laboratory of Chromosome and Cell Biology|
|演題：||Regulations of mitotic processes by nucleosomes — molecular principles and implications in cancer biology and immunology|
Chromosome structure and functions dramatically change during mitosis. Although the nucleosome is a fundamental structural and functional unit of eukaryotic chromatin, its regulatory roles in mitosis are poorly understood. Through comparative chromatin proteomics analysis to identify proteins whose chromatin binding is altered in mitosis, we discovered the novel nucleosome remodeling complex CHIRRC, composed of CDCA7 and HELLS (homolog of plant DDM1), both of which are mutated in the Immunodeficiency, Centromere instability and Facial anomalies (ICF) syndrome. Lymphoblastoid cell lines from ICF patients exhibit hypomethylation and fragility at juxtacentromeric heterochromatin of chromosome 1 and 16. Our finding provides a mechanistic insight into how CDCA7 and HELLS contribute to DNA methylation. We also found that the cytoplasmic DNA sensor, cGAS, a critical component of the innate immune system, gains an access to mitotic chromosomes upon nuclear envelope break down, but its DNA-induced activation is suppressed by the nucleosome. However, when cells are arrested in mitosis by taxol, cGAS slowly becomes activated and promotes apoptosis. Implications of these findings in the ICF syndrome and cancers will be discussed.
|世話人：||〇中西 真 （癌防御シグナル分野）
山梨 裕司 （腫瘍抑制分野）