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PMID: 17227890 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster.

The Journal of cell biology ·Vol. 176 ·No. 2 ·2007-01-15 ·Pages 155-62

Sakaguchi A, Steward R

Abstract

PR-Set7 is a histone methyltransferase that specifically monomethylates histone H4 lysine 20 (K20) and is essential for cell proliferation. Our results show that in PR-Set7 mutants, the DNA damage checkpoint is activated. This phenotype is manifested by reduction in both the mitotic and the S phase indexes, a delay in the progression through early mitosis, and strong reduction of cyclin B. Furthermore, in a double mutant of PR-Set7 and mei-41 (the fly ATR orthologue), the abnormalities of mitotic progression and the cyclin B protein level were rescued. PR-Set7 also showed a defect in chromosome condensation that was enhanced in the double mutant. We therefore propose that monomethylated H4K20 is involved in the maintenance of proper higher order structure of DNA and is consequently essential for chromosome condensation.

MeSH Terms
Anaphase-Promoting Complex-Cyclosome Animals Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome Brain/cytology,metabolism Cell Cycle/genetics,physiology Cell Cycle Proteins/genetics,metabolism Checkpoint Kinase 1 Chromosome Aberrations Cyclin B/genetics,metabolism DNA Breaks, Double-Stranded/radiation effects DNA Damage Down-Regulation Drosophila Proteins/deficiency,genetics,metabolism Drosophila melanogaster/cytology,genetics,metabolism Histone-Lysine N-Methyltransferase/deficiency,genetics,metabolism Histones/analysis,metabolism Lysine/metabolism Methylation Mitosis/genetics,physiology Mutation Neurons/chemistry,cytology Protein Kinases/deficiency,genetics Protein Serine-Threonine Kinases/deficiency,genetics Ubiquitin-Protein Ligase Complexes/genetics,metabolism
Chemicals
Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome Cdc27 protein, Drosophila Cell Cycle Proteins Cyclin B Drosophila Proteins Histones Histone-Lysine N-Methyltransferase PR-Set7 protein, Drosophila Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Protein Kinases Checkpoint Kinase 1 Mei-41 protein, Drosophila Protein Serine-Threonine Kinases Lysine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sakaguchi Ayako
Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Steward Ruth
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200607178
Published
2007-01-15
Pages
155-62
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2063935
Subset
IM
Grants
NICHD NIH HHS · R01 HD018055 · United States
NICHD NIH HHS · R56 HD018055 · United States
NICHD NIH HHS · HD 18055 · United States
External Links
PubMed source DOI: 10.1083/jcb.200607178 PMC Full Text View journal details
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