The fission yeast spSet1p is a histone H3-K4 methyltransferase that functions in telomere maintenance and DNA repair in an ATM kinase Rad3-dependent pathway

Junko Kanoh; Stefania Francesconi; Ada Collura; Vera Schramke; Fuyuki Ishikawa; Giuseppe Baldacci; Vincent Géli

doi:10.1016/s0022-2836(03)00030-5

The fission yeast spSet1p is a histone H3-K4 methyltransferase that functions in telomere maintenance and DNA repair in an ATM kinase Rad3-dependent pathway

J Mol Biol. 2003 Feb 28;326(4):1081-94. doi: 10.1016/s0022-2836(03)00030-5.

Authors

Junko Kanoh¹, Stefania Francesconi, Ada Collura, Vera Schramke, Fuyuki Ishikawa, Giuseppe Baldacci, Vincent Géli

Affiliation

¹ Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.

PMID: 12589755
DOI: 10.1016/s0022-2836(03)00030-5

Abstract

We have characterized spSet1p, the Schizosaccharomyces pombe ortholog of the budding yeast histone H3 methyltransferase Set1p. SpSet1p catalyzes methylation of H3 at K4, in vivo and in vitro. Deleting spset1 partially affects telomeric and centromeric silencing. Strikingly, lack of spSet1p causes elongation of telomeres in wild-type cells and in most DNA damage checkpoint rad mutant cells, but not in cells lacking the ATM kinase Rad3 or its associated protein Rad26. Interestingly, spset1 deletion specifically causes a reduction in sensitivity to ultraviolet radiation of the PCNA-like checkpoint mutants hus1 and rad1, but not of cells devoid of Rad3. This partial suppression was not due to restoration of checkpoint function or to transcriptional induction of DNA repair genes. Moreover, spset1 allows recovery specifically of the crb2 checkpoint mutant upon treatment with the replication inhibitor hydroxyurea but not upon UV irradiation. Nevertheless, the pathway induced in spset1 cells cannot substitute for the Mus81/Rqh1 DNA damage tolerance pathway. Our results suggest that SpSet1p and the ATM kinase Rad3 function in a common genetic pathway linking chromatin to telomere length regulation and DNA repair.

Publication types

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

MeSH terms

Antineoplastic Agents / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Survival
Centromere / metabolism
Checkpoint Kinase 2
DNA Damage
DNA Repair
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Gene Silencing / physiology
Genes, cdc
Histone-Lysine N-Methyltransferase
Histones / metabolism
Humans
Hydroxyurea / metabolism
Methylation
Methyltransferases / genetics
Methyltransferases / metabolism*
Protein Kinases / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism
Schizosaccharomyces / enzymology
Schizosaccharomyces pombe Proteins / chemistry
Schizosaccharomyces pombe Proteins / genetics
Schizosaccharomyces pombe Proteins / metabolism*
Telomere / metabolism*
Transcription Factors / chemistry
Transcription Factors / genetics
Transcription Factors / metabolism*
Ultraviolet Rays

Substances

Antineoplastic Agents
Cell Cycle Proteins
DNA-Binding Proteins
Histones
Saccharomyces cerevisiae Proteins
Schizosaccharomyces pombe Proteins
Transcription Factors
hus1 protein, S pombe
Methyltransferases
Histone-Lysine N-Methyltransferase
SET1 protein, S cerevisiae
Set1 protein, S pombe
Protein Kinases
Checkpoint Kinase 2
rad3 protein, S pombe
Hydroxyurea