title: Eukaryotic replisome components cooperate to process histones during chromosome replication.
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.
authors.affiliation: Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Foltman
authors.forename: Cecile
authors.initials: C
authors.lastname: Evrin
authors.forename: Giacomo
authors.initials: G
authors.lastname: De Piccoli
authors.forename: Richard C
authors.initials: RC
authors.lastname: Jones
authors.forename: Rick D
authors.initials: RD
authors.lastname: Edmondson
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katou
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nakato
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Karim
authors.initials: K
authors.lastname: Labib
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D018741:Replication Origin; D051818:Replication Protein C / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism; D000099272:Replisomes
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D006609:High Mobility Group Proteins; D056488:Histone Chaperones; D006657:Histones; D009097:Multienzyme Complexes; D021122:Protein Subunits; D051818:Replication Protein C; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; D000099272:Replisomes; C092693:CTF18 protein, S cerevisiae; C541535:FACT protein, S cerevisiae; C069199:MCM2 protein, S cerevisiae