Eukaryotic Replisome Components Cooperate to Process Histones During Chromosome Replication

SummaryDNA 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.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► FACT associates with the replisome, but not with the Mcm2-7 helicase, at origins
► Mcm2 and FACT bind together to histones released from chromatin
► Mcm2 has a conserved histone-binding motif in its amino terminal tail
► Histone binding by Mcm2 contributes to the efficacious replication of chromatin