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'PIPs' in DNA polymerase: PCNA interaction affairs.

Narottam Acharya1, Shraddheya Kumar Patel1, Satya Ranjan Sahu1

  • 1Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar 751023, India.

Biochemical Society Transactions
|November 16, 2020
PubMed
Summary

Proliferating cell nuclear antigen (PCNA) interacts with DNA polymerases via PIP motifs for efficient DNA synthesis. This review explores these interactions and proposes two positioning modes for DNA polymerases on PCNA.

Keywords:
DNA polymerasesDNA replication and recommbinationPCNAmutagenesisproten-protein interactiontranslesion DNA synthesis

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Proliferating cell nuclear antigen (PCNA) is a homotrimeric ring crucial for DNA replication.
  • PCNA features hydrophobic pockets that bind partner proteins via a specific motif.
  • PCNA interacting proteins (PIPs) contain an eight-amino-acid PIP motif that stabilizes PCNA interactions.

Purpose of the Study:

  • To review the current understanding of DNA polymerase-PCNA interactions.
  • To elucidate the functional significance of these interactions in DNA synthesis.
  • To identify existing knowledge gaps and propose new models for DNA polymerase positioning on PCNA.

Main Methods:

  • Literature review of published studies on PCNA and DNA polymerase interactions.
  • Analysis of the structural and functional roles of PIP motifs.
  • Theoretical modeling to propose modes of DNA polymerase positioning on PCNA.

Main Results:

  • Multiple PIP motifs have been identified in eukaryotic DNA polymerases.
  • The interaction is essential for processive DNA synthesis.
  • Existing models may not fully account for the complexity of the replisome.

Conclusions:

  • The PCNA-DNA polymerase interaction is fundamental to DNA replication fidelity and efficiency.
  • Two distinct modes of DNA polymerase positioning on PCNA are proposed to explain their roles in the replisome.
  • Further research is needed to fully understand the dynamics and regulation of these interactions within the replication machinery.