Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells

Daniela Cornacchia; Vishnu Dileep; Jean-Pierre Quivy; Rossana Foti; Federico Tili; Rachel Santarella-Mellwig; Claude Antony; Geneviève Almouzni; David M. Gilbert; Sara B C Buonomo

doi:10.1038/emboj.2012.214

Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells

Daniela Cornacchia, Vishnu Dileep, Jean-Pierre Quivy, Rossana Foti, Federico Tili, Rachel Santarella-Mellwig, Claude Antony, Geneviève Almouzni, David M. Gilbert, Sara B C Buonomo

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells.

Original language	English
Pages (from-to)	3678-3690
Number of pages	13
Journal	EMBO Journal
Volume	31
Issue number	18
Early online date	31 Jul 2012
DOIs	https://doi.org/10.1038/emboj.2012.214
Publication status	Published - 12 Sept 2012

Keywords / Materials (for Non-textual outputs)

Alleles
Animals
Cell Cycle
DNA Replication
Female
G1 Phase
Gene Expression Regulation
Genome
Genotype
Heterochromatin
Kinetics
Male
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Nuclear Matrix
S Phase
Telomere-Binding Proteins
Transcription, Genetic
Journal Article
Research Support, Non-U.S. Gov't

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@article{4fc54be7712b48f29e0ac30265faba41,

title = "Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells",

abstract = "The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells.",

keywords = "Alleles, Animals, Cell Cycle, DNA Replication, Female, G1 Phase, Gene Expression Regulation, Genome, Genotype, Heterochromatin, Kinetics, Male, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Nuclear Matrix, S Phase, Telomere-Binding Proteins, Transcription, Genetic, Journal Article, Research Support, Non-U.S. Gov't",

author = "Daniela Cornacchia and Vishnu Dileep and Jean-Pierre Quivy and Rossana Foti and Federico Tili and Rachel Santarella-Mellwig and Claude Antony and Genevi{\`e}ve Almouzni and Gilbert, {David M.} and Buonomo, {Sara B C}",

year = "2012",

month = sep,

day = "12",

doi = "10.1038/emboj.2012.214",

language = "English",

volume = "31",

pages = "3678--3690",

journal = "EMBO Journal",

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TY - JOUR

T1 - Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells

AU - Cornacchia, Daniela

AU - Dileep, Vishnu

AU - Quivy, Jean-Pierre

AU - Foti, Rossana

AU - Tili, Federico

AU - Santarella-Mellwig, Rachel

AU - Antony, Claude

AU - Almouzni, Geneviève

AU - Gilbert, David M.

AU - Buonomo, Sara B C

PY - 2012/9/12

Y1 - 2012/9/12

N2 - The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells.

AB - The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells.

KW - Alleles

KW - Animals

KW - Cell Cycle

KW - DNA Replication

KW - Female

KW - G1 Phase

KW - Gene Expression Regulation

KW - Genome

KW - Genotype

KW - Heterochromatin

KW - Kinetics

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Microscopy, Confocal

KW - Nuclear Matrix

KW - S Phase

KW - Telomere-Binding Proteins

KW - Transcription, Genetic

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/emboj.2012.214

DO - 10.1038/emboj.2012.214

M3 - Article

C2 - 22850673

SN - 0261-4189

VL - 31

SP - 3678

EP - 3690

JO - EMBO Journal

JF - EMBO Journal

IS - 18

ER -

Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

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