Eukaryotic replisome components cooperate to process histones during chromosome replication

Cell Rep. 2013 Mar 28;3(3):892-904. doi: 10.1016/j.celrep.2013.02.028. Epub 2013 Mar 14.

Abstract

DNA unwinding at eukaryotic replication forks displaces parental histones, which must be redeposited onto nascent DNA in order to preserve chromatin structure. By screening systematically for replisome components that pick up histones released from chromatin into a yeast cell extract, we found that the Mcm2 helicase subunit binds histones cooperatively with the FACT (facilitiates chromatin transcription) complex, which helps to re-establish chromatin during transcription. FACT does not associate with the Mcm2-7 helicase at replication origins during G1 phase but is subsequently incorporated into the replisome progression complex independently of histone binding and uniquely among histone chaperones. The amino terminal tail of Mcm2 binds histones via a conserved motif that is dispensable for DNA synthesis per se but helps preserve subtelomeric chromatin, retain the 2 micron minichromosome, and support growth in the absence of Ctf18-RFC. Our data indicate that the eukaryotic replication and transcription machineries use analogous assemblies of multiple chaperones to preserve chromatin integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomes / metabolism*
  • DNA Replication*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • G1 Phase
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism
  • Histone Chaperones / metabolism
  • Histones / metabolism*
  • Molecular Sequence Data
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Replication Origin
  • Replication Protein C / genetics
  • Replication Protein C / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • CTF18 protein, S cerevisiae
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • FACT protein, S cerevisiae
  • High Mobility Group Proteins
  • Histone Chaperones
  • Histones
  • Multienzyme Complexes
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • DNA synthesome
  • DNA-Directed DNA Polymerase
  • Replication Protein C
  • MCM2 protein, S cerevisiae