关键词: Bridging fiber Centriolar satellites Chromosome alignment Ciliogenesis DPF3 Genomic instability Mitosis

Mesh : Animals Humans Mice Axoneme / metabolism Centrioles / metabolism Centrosome / metabolism Cilia / metabolism DNA-Binding Proteins / metabolism genetics Genomic Instability HeLa Cells Kinetochores / metabolism Mitosis Spindle Apparatus / metabolism Transcription Factors / metabolism genetics

来  源:   DOI:10.1242/jcs.261744   PDF(Pubmed)

Abstract:
DPF3, along with other subunits, is a well-known component of the BAF chromatin remodeling complex, which plays a key role in regulating chromatin remodeling activity and gene expression. Here, we elucidated a non-canonical localization and role for DPF3. We showed that DPF3 dynamically localizes to the centriolar satellites in interphase and to the centrosome, spindle midzone and bridging fiber area, and midbodies during mitosis. Loss of DPF3 causes kinetochore fiber instability, unstable kinetochore-microtubule attachment and defects in chromosome alignment, resulting in altered mitotic progression, cell death and genomic instability. In addition, we also demonstrated that DPF3 localizes to centriolar satellites at the base of primary cilia and is required for ciliogenesis by regulating axoneme extension. Taken together, these findings uncover a moonlighting dual function for DPF3 during mitosis and ciliogenesis.
摘要:
DPF3,以及其他亚基,是BAF染色质重塑复合物的众所周知的成分,在调节染色质重塑活性和基因表达中起关键作用。这里,我们阐明了DPF3的非规范定位和作用。我们表明DPF3动态定位在相间和中心体的中心卫星上,有丝分裂期间纺锤体中区/桥接纤维区和中体。DPF3的损失导致K-光纤不稳定,染色体排列中不稳定的动粒-微管附着和缺陷,从而导致有丝分裂进程的改变,细胞死亡和基因组不稳定。此外,我们还证明了DPF3在初级纤毛的基础上位于中心摩尔卫星中,并且通过调节轴突延伸而成为纤毛发生所必需的。一起,这些发现揭示了DPF3在有丝分裂和纤毛发生过程中的月光双重功能。
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