In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 5 ( 2023-5-19), p. e0285337-
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 PCNA ΔSL47 structure shows the potential distortion of the central loop and reduced hydrophobicity. PCNA ΔSL47 shows a defective interaction with PCNA WT leading to defects in homo-trimerization in vitro . PCNA ΔSL47 is defective in the FEN1 and LIG1 interaction. PCNA ubiquitination and DNA-RNA hybrid processing are defective in PCNA ΔSL47 -expressing cells. Accordingly, PCNA ΔSL47 -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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0285337
DOI:
10.1371/journal.pone.0285337.g001
DOI:
10.1371/journal.pone.0285337.g002
DOI:
10.1371/journal.pone.0285337.g003
DOI:
10.1371/journal.pone.0285337.g004
DOI:
10.1371/journal.pone.0285337.g005
DOI:
10.1371/journal.pone.0285337.g006
DOI:
10.1371/journal.pone.0285337.s001
DOI:
10.1371/journal.pone.0285337.s002
DOI:
10.1371/journal.pone.0285337.s003
DOI:
10.1371/journal.pone.0285337.s004
DOI:
10.1371/journal.pone.0285337.s005
DOI:
10.1371/journal.pone.0285337.s006
DOI:
10.1371/journal.pone.0285337.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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