Unit of Molecular Genetics of Aging, Department of Ecology and Biology, University of Tuscia, 01100 Viterbo, Italy.
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Equipe Labellisée Ligue contre le Cancer (IGBMC), CNRS/INSERM/University of Strasbourg, BP163, Illkirch Cedex, 67404 Strasbourg, France.
Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30498-30508. doi: 10.1073/pnas.2006543117. Epub 2020 Nov 16.
Cytokinesis is monitored by a molecular machinery that promotes the degradation of the intercellular bridge, a transient protein structure connecting the two daughter cells. Here, we found that CSA and CSB, primarily defined as DNA repair factors, are located at the midbody, a transient structure in the middle of the intercellular bridge, where they recruit CUL4 and MDM2 ubiquitin ligases and the proteasome. As a part of this molecular machinery, CSA and CSB contribute to the ubiquitination and the degradation of proteins such as PRC1, the Protein Regulator of Cytokinesis, to ensure the correct separation of the two daughter cells. Defects in CSA or CSB result in perturbation of the abscission leading to the formation of long intercellular bridges and multinucleated cells, which might explain part of the Cockayne syndrome phenotypes. Our results enlighten the role played by CSA and CSB as part of a ubiquitin/proteasome degradation process involved in transcription, DNA repair, and cell division.
细胞分裂是由一种分子机制来监控的，该机制能促进细胞间桥的降解，细胞间桥是连接两个子细胞的短暂的蛋白质结构。在这里，我们发现 CSA 和 CSB 主要被定义为 DNA 修复因子，它们位于中间体（细胞间桥的中间的短暂结构），在那里它们招募 CUL4 和 MDM2 泛素连接酶和蛋白酶体。作为这个分子机制的一部分，CSA 和 CSB 有助于 PRC1（细胞分裂的蛋白调节剂）等蛋白质的泛素化和降解，以确保两个子细胞的正确分离。CSA 或 CSB 的缺陷导致胞质分裂的干扰，导致长细胞间桥和多核细胞的形成，这可能解释了 Cockayne 综合征表型的一部分。我们的结果阐明了 CSA 和 CSB 作为涉及转录、DNA 修复和细胞分裂的泛素/蛋白酶体降解过程的一部分所发挥的作用。
