mRNA 加工因子 CstF-50 和泛素伴侣因子 p97 是 BRCA1/BARD1 共因子，参与 DNA 损伤反应过程中的染色质重塑。
mRNA Processing Factor CstF-50 and Ubiquitin Escort Factor p97 Are BRCA1/BARD1 Cofactors Involved in Chromatin Remodeling during the DNA Damage Response.
机构信息
Chemistry Department, Hunter College and Biochemistry Program, Graduate Center, City University of New York, New York, New York, USA.
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
出版信息
Mol Cell Biol. 2018 Jan 29;38(4). doi: 10.1128/MCB.00364-17. Print 2018 Feb 15.
The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. In this study, we provide evidence of the roles of the polyadenylation factor cleavage stimulation factor 50 (CstF-50) and the ubiquitin (Ub) escort factor p97 as cofactors of BRCA1/BARD1 E3 Ub ligase, facilitating chromatin remodeling during the DNA damage response (DDR). CstF-50 and p97 formed complexes with BRCA1/BARD1, Ub, and some BRCA1/BARD1 substrates, such as RNA polymerase (RNAP) II and histones. Furthermore, CstF-50 and p97 had an additive effect on the activation of the ubiquitination of these BRCA1/BARD1 substrates during DDR. Importantly, as a result of these functional interactions, BRCA1/BARD1/CstF-50/p97 had a specific effect on the chromatin structure of genes that were differentially expressed. This study provides new insights into the roles of RNA processing, BRCA1/BARD1, the Ub pathway, and chromatin structure during DDR.
细胞对 DNA 损伤的反应是一种复杂的机制，涉及几个途径的相互作用。在这项研究中，我们提供了多聚腺苷酸化因子切割刺激因子 50（CstF-50）和泛素（Ub）护送因子 p97 作为 BRCA1/BARD1 E3 Ub 连接酶辅助因子的作用证据，在 DNA 损伤反应（DDR）期间促进染色质重塑。CstF-50 和 p97 与 BRCA1/BARD1、Ub 和一些 BRCA1/BARD1 底物（如 RNA 聚合酶（RNAP）II 和组蛋白）形成复合物。此外，CstF-50 和 p97 在 DDR 期间对 BRCA1/BARD1 这些底物的泛素化激活具有附加效应。重要的是，由于这些功能相互作用，BRCA1/BARD1/CstF-50/p97 对差异表达基因的染色质结构具有特异性影响。本研究为 RNA 加工、BRCA1/BARD1、Ub 途径和 DDR 期间的染色质结构的作用提供了新的见解。
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