Histones serine 139 phosphorylation

In Saccharomyces cerevisiae, multiple histone H2A phosphorylation sites have been characterized (Serine 122, Serine 129, Threonine 126) (Wyatt et al, 2003 Harvey et al, 2005 Redon et al, 2006). Histone H2A (S129) is essential for DNA double-strand-break responses (see Section 4) and histone H2A (SI22) is important for survival in the presence of DNA damage (Harvey et al, 2005) (Fig. 2). 

Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome ahgnment, kinetochore disjunction, chromosome segregation. J Cell Biol 153(4) 865-880 Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Alhs CD (2005a) Sterile 20 kinase phospho-rylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell 120(l) 25-36... 

Herrera RE, Chen E, Weinberg RA (1996) Increased histone HI phosphorylation and relaxed chromatin structure in Rb-deficient fibroblasts. Proc Natl Acad Sci USA 93(21) 11510-11515 Hirota T, Lipp JJ, Toh BH, Peters JM (2005) Histone H3 serine 10 phosphorylation by Aurora B causes HPl dissociation from heterochromatin. Nature 438(7071) 1176—1180 Horn PJ, Carruthers LM, Logie C, Hill DA, Solomon MJ, Wade PA, Imbalzano AN, Hansen JC, Peterson CL (2002) Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes. Nat Struct Biol 9(4) 263—267... 

In cells of the mammary gland, either in normal epithelial or in cancerous cells, the packaging of chromosomal DNA into chromatin restricts the access of the transcription machinery, thereby causing transcriptional repression. The basic N-termini of histones are subject to post-translational modifications, including lysine acetylation, lysine and arginine methylation, serine phosphorylation and ubiquitinylation [56]. It has been proposed in the histone code hypothesis that the intricate pattern of modifications of the N-terminal histone tail influences gene regulation [57]. 

The serine phosphorylated in histone I (FI) is one amino acid removed from a basic residue and in proximity to two proline residues (101) ... 

Histone phosphorylation is a common posttranslational modification fond in histones, primarily on the N-terminal tails. Phosphorylation sites include serine and threonine residues, tyrosine phosphorylation has not been observed so far. Some phosphorylation events occur locally whereas others occur globally throughout all chromosomes during specific events like mitosis. Histone phosphorylation is catalyzed by kinases. Removal of the phosphoryl groups is catalyzed by phosphatases. 

Cytoplasmic serine/threonine protein kinases catalyze the transfer of phosphate groups to serine and threonine residues of target proteins. Serine/threonine kinases have been recognized as the products of protooncogenes (e.g., c-mos, c-raj) or as kinases intimately involved with the regulation of serine/threonine kinase activity by cAMP. Some of these kinases specifically phosphorylate cellular structural proteins, such as histone, laminins, etc. Others phosphorylate still more kinases, resulting in either the activation or deactivation of downstream protein kinases. Specific examples in which serine/threonine kinases elicit specific cellular responses are discussed in this chapter. 

Wei Y, Mizzen CA, Cook RG, Gorovsky MA, Allis CD (1998) Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in Tetrahymena. Proc Natl Acad Sci U S A 95 7480-7484... 

Figure 2. Histone H2A variants from yeast Saccharomyces cerevisiae S.c.), fruit fly Drosophila melanogaster D.m ), and human Homo sapiens H.s.). Two conserved domains distinguish H2A.Z-relatives (boxed regions amino acid sequences in the top). H2A.X possesses a conserved C-terminal stretch of four amino acids. The serine (red) becomes phosphorylated at sites of DNA damage. H2A ( Barr body-deficient ) and marcoH2A are present in mammals...

Barber CM et al., report that histone H2A is highly phosphorylated at Serine 1 residues during mitosis in the worm, fly, and mammalian cells (Barber et al, 2004). This phosphorylation by MSKl negatively regulated transcription on chromatin templates (Zhang et al, 2004). 

Histone H2B amino-terminal tail is essential for chromatin condensation (de la Barre et al, 2001). In Xenopus, chicken, and human cells phosphorylation of H2B at Serine 14 by Mstl (Mammalian Sterile Twenty) kinase has been finked to chromatin compaction during apoptosis (Ajiro, 2000 Cheung et al, 2003), and DNA double-strand breaks (Fernandez-Capetillo et al, 2004) (Fig. 2) (Table 1). At late time points after irradiation, phosphorylated H2B (S14) accumulates into... 

Histone H3 (Til) phosphorylation occurs during mitosis by Dlk/ZIP kinase (Dlk Death-associated protein (DAP)-like kinase, ZIP Zipper interacting protein kinase) (Preuss et al, 2003) (Table 1). Histone H3 at Serine 28 is phosphorylated by Aurora B kinase at mitosis and this phosphorylation coincides with chromosome condensation (Goto et al., 1999, Goto et al, 2002) (Fig. 2), (Table 1). Histone H3 (S28) phosphorylation initiates at prophase, whereas histone H3 (SIO) phosphorylation initiates during the late G2 phase (Hendzel et al, 1997). 

Kogel D, Plottner O, Landsberg G, Christian S, Scheidtmann KH (1998) Ooning and characterization of Dlk, a novel serine/threonine kinase that is tightly associated with chromatin and phosphorylates core histones. Oncogene 17(20) 2645-2654... 

Lo WS, Trievel RC, Rojas JR, Duggan L, Hsu JY, Allis CD, Marmorstein R, Berger SL (2000) Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14. Mol Cell 5(6) 917—926... 

Maile T, Kwoczynski S, Katzenberger RJ, Wassarman DA, Sauer E (2004) TAEl activates transcription by phosphorylation of serine 33 in histone H2B. Science 304(5673) 1010-1014... 

Polioudaki H, Markaki Y, Kourmouli N, Dialynas G, Theodoropoulos PA, Singh PB, Georgatos SD (2004) Mitotic phosphorylation of histone H3 at threonine 3. FEBS Lett 560(l-3) 39 4 Preuss U, Landsberg G, Scheidtmann KH (2003) Novel mitosis-specific phosphorylation of histone H3 at Thrll mediated by Dlk/ZIP kinase. Nucleic Acids Res 31(3) 878-885 Prigent C, Dimitrov S (2003) Phosphorylation of serine 10 in histone H3, what for J Cell Sci 116(Pt 18) 3677-3685... 

Rogakou, E.P., Nieves-Neira, W., Boon, C., Pommier, Y., and Bonner, W.M. (2000) Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J. Biol. Chem. 275, 9390-9395. 

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