Regulation of replication fork progression through histone supply and demand.

Anja Groth; Armelle Corpet; Adam J L Cook; Daniele Roche; Jiri Bartek; Jiri Lukas; Geneviève Almouzni

doi:10.1126/science.1148992

Regulation of replication fork progression through histone supply and demand.

Anja Groth, Armelle Corpet, Adam J L Cook, Daniele Roche, Jiri Bartek, Jiri Lukas, Geneviève Almouzni

297 Citations (Scopus)

Abstract

DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork progression and histone supply and demand.

Original language	English
Journal	Science
Volume	318
Issue number	5858
Pages (from-to)	1928-31
Number of pages	3
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1148992
Publication status	Published - 2007

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title = "Regulation of replication fork progression through histone supply and demand.",

abstract = "DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork progression and histone supply and demand.",

author = "Anja Groth and Armelle Corpet and Cook, {Adam J L} and Daniele Roche and Jiri Bartek and Jiri Lukas and Genevi{\`e}ve Almouzni",

note = "Keywords: Cell Cycle Proteins; Chromatin; DNA; DNA Replication; DNA, Single-Stranded; Hela Cells; Histones; Humans; Models, Biological; Molecular Chaperones; Nuclear Proteins; Nucleosomes; RNA Interference; S Phase",

year = "2007",

doi = "10.1126/science.1148992",

language = "English",

volume = "318",

pages = "1928--31",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5858",

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TY - JOUR

T1 - Regulation of replication fork progression through histone supply and demand.

AU - Groth, Anja

AU - Corpet, Armelle

AU - Cook, Adam J L

AU - Roche, Daniele

AU - Bartek, Jiri

AU - Lukas, Jiri

AU - Almouzni, Geneviève

N1 - Keywords: Cell Cycle Proteins; Chromatin; DNA; DNA Replication; DNA, Single-Stranded; Hela Cells; Histones; Humans; Models, Biological; Molecular Chaperones; Nuclear Proteins; Nucleosomes; RNA Interference; S Phase

PY - 2007

Y1 - 2007

N2 - DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork progression and histone supply and demand.

AB - DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork progression and histone supply and demand.

U2 - 10.1126/science.1148992

DO - 10.1126/science.1148992

M3 - Journal article

C2 - 18096807

SN - 0036-8075

VL - 318

SP - 1928

EP - 1931

JO - Science

JF - Science

IS - 5858

ER -

Regulation of replication fork progression through histone supply and demand.

Abstract

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