AI Article Synopsis

  • - PCNA is essential for DNA replication and forms a homotrimer that interacts with proteins like DNA polymerases and ligases to ensure accurate copying of DNA.
  • - The study identifies that specific residues (Ser46-Leu47) in PCNA are crucial for maintaining its structure and function, highlighting the impact of their modification on PCNA's ability to interact with other proteins.
  • - Cells lacking these specific residues show increased DNA damage, evidenced by more single-stranded DNA gaps and sensitivity to DNA-damaging agents, which underscores the importance of these residues in genomic integrity.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10198555PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285337PLOS

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