| Structural highlights
Function
[H2A1_YEAST] Core component of nucleosome which plays a central role in DNA double strand break (DSB) repair. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[1] [2] [3] [4] [H2B1_YEAST] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[5] [6] [7] [8] [9] [10] [11] [12] [13]
Publication Abstract from PubMed
FACT, a heterodimer of Spt16 and Pob3, is an essential histone chaperone. We show that the H2A-H2B binding activity that is central to FACT function resides in short acidic regions near the C termini of each subunit. Mutations throughout these regions affect binding and cause correlated phenotypes that range from mild to lethal, with the largest individual contributions unexpectedly coming from an aromatic residue and a nearby carboxylate residue within each domain. Spt16 and Pob3 bind overlapping sites on H2A-H2B, and Spt16-Pob3 heterodimers simultaneously bind two H2A-H2B dimers, the same stoichiometry as the components of a nucleosome. An Spt16:H2A-H2B crystal structure explains the biochemical and genetic data, provides a model for Pob3 binding, and implies a mechanism for FACT reorganization that we confirm biochemically. Moreover, unexpected similarity to binding of ANP32E and Swr1 with H2A.Z-H2B reveals that diverse H2A-H2B chaperones use common mechanisms of histone binding and regulating nucleosome functions.
FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs.,Kemble DJ, McCullough LL, Whitby FG, Formosa T, Hill CP Mol Cell. 2015 Oct 15;60(2):294-306. doi: 10.1016/j.molcel.2015.09.008. Epub 2015, Oct 8. PMID:26455391[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Downs JA, Lowndes NF, Jackson SP. A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature. 2000 Dec 21-28;408(6815):1001-4. PMID:11140636 doi:10.1038/35050000
- ↑ Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH, Haber JE, Lichten M. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol. 2004 Oct 5;14(19):1703-11. PMID:15458641 doi:10.1016/j.cub.2004.09.047
- ↑ Unal E, Arbel-Eden A, Sattler U, Shroff R, Lichten M, Haber JE, Koshland D. DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell. 2004 Dec 22;16(6):991-1002. PMID:15610741 doi:S1097276504007191
- ↑ Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2006 Jan 26;439(7075):497-501. Epub 2005 Nov 20. PMID:16299494 doi:nature04384
- ↑ Martini EM, Keeney S, Osley MA. A role for histone H2B during repair of UV-induced DNA damage in Saccharomyces cerevisiae. Genetics. 2002 Apr;160(4):1375-87. PMID:11973294
- ↑ Briggs SD, Xiao T, Sun ZW, Caldwell JA, Shabanowitz J, Hunt DF, Allis CD, Strahl BD. Gene silencing: trans-histone regulatory pathway in chromatin. Nature. 2002 Aug 1;418(6897):498. Epub 2002 Jul 14. PMID:12152067 doi:10.1038/nature00970
- ↑ Kao CF, Hillyer C, Tsukuda T, Henry K, Berger S, Osley MA. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev. 2004 Jan 15;18(2):184-95. PMID:14752010 doi:10.1101/gad.1149604
- ↑ Yamashita K, Shinohara M, Shinohara A. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11380-5. Epub 2004 Jul 27. PMID:15280549 doi:10.1073/pnas.0400078101
- ↑ Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005 Jan 14;120(1):25-36. PMID:15652479 doi:S009286740401092X
- ↑ Ahn SH, Henderson KA, Keeney S, Allis CD. H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae. Cell Cycle. 2005 Jun;4(6):780-3. Epub 2005 Jun 14. PMID:15970663
- ↑ Giannattasio M, Lazzaro F, Plevani P, Muzi-Falconi M. The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem. 2005 Mar 18;280(11):9879-86. Epub 2005 Jan 4. PMID:15632126 doi:M414453200
- ↑ Xiao T, Kao CF, Krogan NJ, Sun ZW, Greenblatt JF, Osley MA, Strahl BD. Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol. 2005 Jan;25(2):637-51. PMID:15632065 doi:25/2/637
- ↑ Nathan D, Ingvarsdottir K, Sterner DE, Bylebyl GR, Dokmanovic M, Dorsey JA, Whelan KA, Krsmanovic M, Lane WS, Meluh PB, Johnson ES, Berger SL. Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev. 2006 Apr 15;20(8):966-76. Epub 2006 Apr 5. PMID:16598039 doi:gad.1404206
- ↑ Kemble DJ, McCullough LL, Whitby FG, Formosa T, Hill CP. FACT Disrupts Nucleosome Structure by Binding H2A-H2B with Conserved Peptide Motifs. Mol Cell. 2015 Oct 15;60(2):294-306. doi: 10.1016/j.molcel.2015.09.008. Epub 2015, Oct 8. PMID:26455391 doi:http://dx.doi.org/10.1016/j.molcel.2015.09.008
|
