PCNA 丝氨酸 46 位至亮氨酸 47 位残基对于保持基因组完整性至关重要。
PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity.
机构信息
Institute for Basic Science, Center for Genomic Integrity, Ulsan, Korea.
Department of Biological Sciences, Ulsan National Institute of Science and Technology, College of Information-Bio Convergence Engineering, Ulsan, Korea.
出版信息
PLoS One. 2023 May 19;18(5):e0285337. doi: 10.1371/journal.pone.0285337. eCollection 2023.
Proliferating cell nuclear antigen (PCNA) is a maestro of DNA replication. PCNA forms a homotrimer and interacts with various proteins, such as DNA polymerases, DNA ligase I (LIG1), and flap endonuclease 1 (FEN1) for faithful DNA replication. Here, we identify the crucial role of Ser46-Leu47 residues of PCNA in maintaining genomic integrity using in vitro, and cell-based assays and structural prediction. The predicted PCNAΔSL47 structure shows the potential distortion of the central loop and reduced hydrophobicity. PCNAΔSL47 shows a defective interaction with PCNAWT leading to defects in homo-trimerization in vitro. PCNAΔSL47 is defective in the FEN1 and LIG1 interaction. PCNA ubiquitination and DNA-RNA hybrid processing are defective in PCNAΔSL47-expressing cells. Accordingly, PCNAΔSL47-expressing cells exhibit an increased number of single-stranded DNA gaps and higher levels of γH2AX, and sensitivity to DNA-damaging agents, highlighting the importance of PCNA Ser46-Leu47 residues in maintaining genomic integrity.
增殖细胞核抗原（PCNA）是 DNA 复制的总指挥。PCNA 形成三聚体，并与各种蛋白质相互作用，如 DNA 聚合酶、DNA 连接酶 I（LIG1）和核酸内切酶 1（FEN1），以实现忠实的 DNA 复制。在这里，我们使用体外和基于细胞的测定和结构预测来确定 PCNA 的 Ser46-Leu47 残基在维持基因组完整性方面的关键作用。预测的 PCNAΔSL47 结构显示中央环的潜在变形和疏水性降低。PCNAΔSL47 与 PCNAWT 的相互作用有缺陷，导致体外同源三聚体化缺陷。PCNAΔSL47 与 FEN1 和 LIG1 的相互作用有缺陷。PCNA 泛素化和 DNA-RNA 杂交处理在表达 PCNAΔSL47 的细胞中存在缺陷。因此，表达 PCNAΔSL47 的细胞表现出更多的单链 DNA 缺口和更高水平的 γH2AX，以及对 DNA 损伤剂的敏感性，突出了 PCNA Ser46-Leu47 残基在维持基因组完整性方面的重要性。
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