The histone methyltransferase SET8 is required for S-phase progression.

Stine Jørgensen; Ingegerd Elvers; Morten Beck Trelle; Tobias Menzel; Morten Eskildsen; Ole Nørregaard Jensen; Thomas Helleday; Kristian Helin; Claus Storgaard Sørensen

doi:10.1083/jcb.200706150

The histone methyltransferase SET8 is required for S-phase progression.

Stine Jørgensen, Ingegerd Elvers, Morten Beck Trelle, Tobias Menzel, Morten Eskildsen, Ole Nørregaard Jensen, Thomas Helleday, Kristian Helin, Claus Storgaard Sørensen

163 Citations (Scopus)

Abstract

Chromatin structure and function is influenced by histone posttranslational modifications. SET8 (also known as PR-Set7 and SETD8) is a histone methyltransferase that monomethylates histonfe H4-K20. However, a function for SET8 in mammalian cell proliferation has not been determined. We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. Overall, we show that SET8 is essential for genomic stability in mammalian cells and that decreased expression of SET8 results in DNA damage and Chk1-dependent S-phase arrest.
Udgivelsesdato: 2007-Dec-31

Original language	English
Journal	Journal of Cell Biology
Volume	179
Issue number	7
Pages (from-to)	1337-45
Number of pages	8
ISSN	0021-9525
DOIs	https://doi.org/10.1083/jcb.200706150
Publication status	Published - 2008

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10.1083/jcb.200706150

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@article{7895c630d94311dcbee902004c4f4f50,

title = "The histone methyltransferase SET8 is required for S-phase progression.",

abstract = "Chromatin structure and function is influenced by histone posttranslational modifications. SET8 (also known as PR-Set7 and SETD8) is a histone methyltransferase that monomethylates histonfe H4-K20. However, a function for SET8 in mammalian cell proliferation has not been determined. We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. Overall, we show that SET8 is essential for genomic stability in mammalian cells and that decreased expression of SET8 results in DNA damage and Chk1-dependent S-phase arrest. Udgivelsesdato: 2007-Dec-31",

author = "Stine J{\o}rgensen and Ingegerd Elvers and Trelle, {Morten Beck} and Tobias Menzel and Morten Eskildsen and Jensen, {Ole N{\o}rregaard} and Thomas Helleday and Kristian Helin and S{\o}rensen, {Claus Storgaard}",

year = "2008",

doi = "10.1083/jcb.200706150",

language = "English",

volume = "179",

pages = "1337--45",

journal = "Journal of Cell Biology",

issn = "0021-9525",

publisher = "Rockefeller University Press",

number = "7",

}

TY - JOUR

T1 - The histone methyltransferase SET8 is required for S-phase progression.

AU - Jørgensen, Stine

AU - Elvers, Ingegerd

AU - Trelle, Morten Beck

AU - Menzel, Tobias

AU - Eskildsen, Morten

AU - Jensen, Ole Nørregaard

AU - Helleday, Thomas

AU - Helin, Kristian

AU - Sørensen, Claus Storgaard

PY - 2008

Y1 - 2008

N2 - Chromatin structure and function is influenced by histone posttranslational modifications. SET8 (also known as PR-Set7 and SETD8) is a histone methyltransferase that monomethylates histonfe H4-K20. However, a function for SET8 in mammalian cell proliferation has not been determined. We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. Overall, we show that SET8 is essential for genomic stability in mammalian cells and that decreased expression of SET8 results in DNA damage and Chk1-dependent S-phase arrest. Udgivelsesdato: 2007-Dec-31

AB - Chromatin structure and function is influenced by histone posttranslational modifications. SET8 (also known as PR-Set7 and SETD8) is a histone methyltransferase that monomethylates histonfe H4-K20. However, a function for SET8 in mammalian cell proliferation has not been determined. We show that small interfering RNA inhibition of SET8 expression leads to decreased cell proliferation and accumulation of cells in S phase. This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. Furthermore, we find that SET8 interacts with proliferating cell nuclear antigen through a conserved motif, and SET8 is required for DNA replication fork progression. Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. Overall, we show that SET8 is essential for genomic stability in mammalian cells and that decreased expression of SET8 results in DNA damage and Chk1-dependent S-phase arrest. Udgivelsesdato: 2007-Dec-31

U2 - 10.1083/jcb.200706150

DO - 10.1083/jcb.200706150

M3 - Journal article

C2 - 18166648

SN - 0021-9525

VL - 179

SP - 1337

EP - 1345

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 7

ER -