Protein Section, Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Mol Cell Biol. 2012 May;32(10):1844-54. doi: 10.1128/MCB.06429-11. Epub 2012 Mar 5.
Proliferating cell nuclear antigen (PCNA) is a ubiquitous protein that interacts with multiple partners and regulates nuclear activities, including chromatin assembly, histone modifications, replication, and DNA damage repair. The role of specific partners in regulating PCNA activities is not fully understood. Here we identify the nucleosome binding protein HMGN1 as a new PCNA-interacting protein that enhances the binding of PCNA to chromatin but not to purified DNA. Two tetrapeptides in the conservative domain of HMGN1 contain amino acids necessary for the binding of HMGN1 to PCNA. Deletion of both tetrapeptides abolishes the HMGN1-PCNA interaction. PCNA preferentially binds to the linker DNA adjacent to an HMGN-containing nucleosome. In living cells, loss of HMGN1 decreases the rate of PCNA recruitment to damaged DNA sites. Our study identifies a new factor that facilitates the interaction of PCNA with chromatin and provides insights into mechanisms whereby nucleosome binding architectural proteins affect the cellular phenotype.
增殖细胞核抗原（PCNA）是一种普遍存在的蛋白质，可与多种伴侣相互作用，调节核活动，包括染色质组装、组蛋白修饰、复制和 DNA 损伤修复。特定伴侣在调节 PCNA 活性中的作用尚不完全清楚。在这里，我们确定核小体结合蛋白 HMGN1 为一种新的 PCNA 相互作用蛋白，可增强 PCNA 与染色质的结合，但与纯化的 DNA 不结合。HMGN1 保守结构域中的两个四肽包含与 HMGN1 与 PCNA 结合所必需的氨基酸。删除这两个四肽会使 HMGN1-PCNA 相互作用消失。PCNA 优先结合到含有 HMGN 的核小体相邻的连接 DNA 上。在活细胞中，HMGN1 的缺失会降低 PCNA 募集到受损 DNA 位点的速度。我们的研究确定了一种新的因子，该因子促进了 PCNA 与染色质的相互作用，并深入了解了核小体结合结构蛋白如何影响细胞表型的机制。
