PCNA cycling dynamics during DNA replication and repair in mammals

Trends Genet. 2024 Jun;40(6):526-539. doi: 10.1016/j.tig.2024.02.006. Epub 2024 Mar 13.

Abstract

Proliferating cell nuclear antigen (PCNA) is a eukaryotic replicative DNA clamp. Furthermore, DNA-loaded PCNA functions as a molecular hub during DNA replication and repair. PCNA forms a closed homotrimeric ring that encircles the DNA, and association and dissociation of PCNA from DNA are mediated by clamp-loader complexes. PCNA must be actively released from DNA after completion of its function. If it is not released, abnormal accumulation of PCNA on chromatin will interfere with DNA metabolism. ATAD5 containing replication factor C-like complex (RLC) is a PCNA-unloading clamp-loader complex. ATAD5 deficiency causes various DNA replication and repair problems, leading to genome instability. Here, we review recent progress regarding the understanding of the action mechanisms of PCNA unloading complex in DNA replication/repair pathways.

Keywords: ATAD5; DNA repair; DNA replication; PCNA; RFC.

Publication types

  • Review

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA / genetics
  • DNA / metabolism
  • DNA Repair* / genetics
  • DNA Replication* / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genomic Instability / genetics
  • Humans
  • Mammals* / genetics
  • Proliferating Cell Nuclear Antigen* / genetics
  • Proliferating Cell Nuclear Antigen* / metabolism

Substances

  • Proliferating Cell Nuclear Antigen
  • Chromatin
  • DNA-Binding Proteins
  • DNA
  • ATPases Associated with Diverse Cellular Activities
  • ATAD5 protein, human