Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster.
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.
Sakaguchi
Ayako
A
Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Steward
Ruth
R
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D002869:Chromosome Aberrations; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000032:analysis / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000737:chemistry / Q000166:cytology; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577365:Cdc27 protein, Drosophila; D018797:Cell Cycle Proteins; D019926:Cyclin B; D029721:Drosophila Proteins; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; C498199:PR-Set7 protein, Drosophila; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D008239:Lysine