1. PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity.
- Author
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Kim, Sangin, Kim, Yeongjae, Kim, Youyoung, Yoon, Suhyeon, Lee, Kyoo-young, Lee, Yoonsung, Kang, Sukhyun, Myung, Kyungjae, and Oh, Chang-Kyu
- Subjects
PROLIFERATING cell nuclear antigen ,DNA polymerases ,SINGLE-stranded DNA ,DNA replication - 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. 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. [ABSTRACT FROM AUTHOR]- Published
- 2023
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