ゼブラフィッシュ網膜においてBanpはDNA損傷応答と染色体分離を制御することで、細胞周期の進行と細胞生存を促進する。 Banp Regulates DNA Damage Response and Chromosome Segregation to Promote Cell-cycle Progression and Cell Survival in Zebrafish Retina

収集根拠 : 博士論文（自動収集）

資料形態 : テキストデータ

コレクション : 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文

Btg3 associated nuclear protein (Banp) was initially identified as a nuclear matrix associated protein and is a tumor suppressor. Recently it was reported that Banp binds to the CGCG element containing motif enriched near the transcription initiation site of CpG island promoters, namely Banp motif, promotes the transcription in a DNA methylation dependent manner, and controls metabolic genes in pluripotent stem and differentiated neuronal cells. However, cellular roles of Banp in embryonic development remains to be elucidated. Here we report a novel role of Banp in cell-cycle progression and cell survival of zebrafish retinal progenitor cells (RPCs). In zebrafish banprw337 mutants, retinal progenitor cells showed mitotic cell accumulation and subsequent apoptosis. DNA replication stress and tp53-dependent DNA damage response were activated in banprw337 mutants. Inhibition of Tp53 significantly rescued apoptosis but not mitotic defect and DNA double strand break accumulation, suggesting that Banp is required for maintaining integrity of DNA during segregation and replication. Furthermore, live imaging of mitosis in banp morphant retinas revealed that chromosome segregation was not smoothly processed from prometaphase to anaphase, leading to prolonged M-phase. Bulk RNA-seq analysis show that mRNA expression of two chromosomal segregation regulators, cenpt and ncapg, were decreased in banprw337 mutants. Furthermore, ATAC-seq analysis showed that chromatin near their transcription start site was closed in banprw337 mutants and indeed Banp motif was found in this chromatin-closed region, suggesting that Banp directly regulates cenpt and ncapg transcription via Banp motif to promote chromosome segregation during mitosis. Our findings reveal that Banp is required for cell-cycle progression and cell survival by regulating replicative DNA damage response and mitotic chromosome segregation.