Histone H4 and the maintenance of genome integrity - PubMed (original) (raw)
. 1995 Jul 15;9(14):1716-27.
doi: 10.1101/gad.9.14.1716.
Affiliations
- PMID: 7622036
- DOI: 10.1101/gad.9.14.1716
Free article
Histone H4 and the maintenance of genome integrity
P C Megee et al. Genes Dev. 1995.
Free article
Abstract
The normal progression of Saccharomyces cerevisiae through nuclear division requires the function of the amino-terminal domain of histone H4. Mutations that delete the domain, or alter 4 conserved lysine residues within the domain, cause a marked delay during the G2+M phases of the cell cycle. Site-directed mutagenesis of single and multiple lysine residues failed to map this phenotype to any particular site; the defect was only observed when all four lysines were mutated. Starting with a quadruple lysine-to-glutamine substitution allele, the insertion of a tripeptide containing a single extra lysine residue suppressed the G2+M cell cycle defect. Thus, the amino-terminal domain of histone H4 has novel genetic functions that depend on the presence of lysine per se, and not a specific primary peptide sequence. To determine the nature of this function, we examined H4 mutants that were also defective for G2/M checkpoint pathways. Disruption of the mitotic spindle checkpoint pathway had no effect on the phenotype of the histone amino-terminal domain mutant. However, disruption of RAD9, which is part of the pathway that monitors DNA integrity, caused precocious progression of the H4 mutant through nuclear division and increased cell death. These results indicate that the lysine-dependent function of histone H4 is required for the maintenance of genome integrity, and that DNA damage resulting from the loss of this function activates the RAD9-dependent G2/M checkpoint pathway.
Similar articles
- Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation.
Megee PC, Morgan BA, Mittman BA, Smith MM. Megee PC, et al. Science. 1990 Feb 16;247(4944):841-5. doi: 10.1126/science.2106160. Science. 1990. PMID: 2106160 - Histone H4, the cell cycle and a question of integrity.
Turner BM. Turner BM. Bioessays. 1995 Dec;17(12):1013-5. doi: 10.1002/bies.950171204. Bioessays. 1995. PMID: 8634061 Review. - The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression.
Morgan BA, Mittman BA, Smith MM. Morgan BA, et al. Mol Cell Biol. 1991 Aug;11(8):4111-20. doi: 10.1128/mcb.11.8.4111-4120.1991. Mol Cell Biol. 1991. PMID: 2072911 Free PMC article. - Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9.
Wysocki R, Javaheri A, Allard S, Sha F, Côté J, Kron SJ. Wysocki R, et al. Mol Cell Biol. 2005 Oct;25(19):8430-43. doi: 10.1128/MCB.25.19.8430-8443.2005. Mol Cell Biol. 2005. PMID: 16166626 Free PMC article. - Genome protection: histone H4 and beyond.
Kumar K, Moirangthem R, Kaur R. Kumar K, et al. Curr Genet. 2020 Oct;66(5):945-950. doi: 10.1007/s00294-020-01088-6. Epub 2020 Jun 17. Curr Genet. 2020. PMID: 32556547 Free PMC article. Review.
Cited by
- A crucial role for dynamic expression of components encoding the negative arm of the circadian clock.
Wang B, Zhou X, Kettenbach AN, Mitchell HD, Markillie LM, Loros JJ, Dunlap JC. Wang B, et al. Nat Commun. 2023 Jun 8;14(1):3371. doi: 10.1038/s41467-023-38817-7. Nat Commun. 2023. PMID: 37291101 Free PMC article. - Altered Epigenetic Profiles in the Placenta of Preeclamptic and Intrauterine Growth Restriction Patients.
Norton C, Clarke D, Holmstrom J, Stirland I, Reynolds PR, Jenkins TG, Arroyo JA. Norton C, et al. Cells. 2023 Apr 11;12(8):1130. doi: 10.3390/cells12081130. Cells. 2023. PMID: 37190039 Free PMC article. - Structure and function of the Orc1 BAH-nucleosome complex.
De Ioannes P, Leon VA, Kuang Z, Wang M, Boeke JD, Hochwagen A, Armache KJ. De Ioannes P, et al. Nat Commun. 2019 Jul 1;10(1):2894. doi: 10.1038/s41467-019-10609-y. Nat Commun. 2019. PMID: 31263106 Free PMC article. - A Failsafe for Sensing Chromatid Tension in Mitosis with the Histone H3 Tail in Saccharomyces cerevisiae.
Buehl CJ, Deng X, Luo J, Buranasudja V, Hazbun T, Kuo MH. Buehl CJ, et al. Genetics. 2018 Feb;208(2):565-578. doi: 10.1534/genetics.117.300606. Epub 2017 Dec 14. Genetics. 2018. PMID: 29242290 Free PMC article. - Structure, function and regulation of jade family PHD finger 1 (JADE1).
Panchenko MV. Panchenko MV. Gene. 2016 Sep 1;589(1):1-11. doi: 10.1016/j.gene.2016.05.002. Epub 2016 May 4. Gene. 2016. PMID: 27155521 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials