The Fork Protection Complex: A Regulatory Hub at the Head of the Replisome

Subcell Biochem. 2022:99:83-107. doi: 10.1007/978-3-031-00793-4_3.

Abstract

As well as accurately duplicating DNA, the eukaryotic replisome performs a variety of other crucial tasks to maintain genomic stability. For example, organizational elements, like cohesin, must be transferred from the front of the fork to the new strands, and when there is replication stress, forks need to be protected and checkpoint signalling activated. The Tof1-Csm3 (or Timeless-Tipin in humans) Fork Protection Complex (FPC) ensures efficient replisome progression and is required for a range of replication-associated activities. Recent studies have begun to reveal the structure of this complex, and how it functions within the replisome to perform its diverse roles. The core of the FPC acts as a DNA grip on the front of the replisome to regulate fork progression. Other flexibly linked domains and motifs mediate interactions with proteins and specific DNA structures, enabling the FPC to act as a hub at the head of the replication fork.

Keywords: Cohesin; DNA replication; Fork protection complex (FPC); Helicase; Polymerase; Replisome; Timeless; Tipin.

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Replication*
  • DNA-Binding Proteins* / metabolism
  • Humans

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins