Histone damage

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...

Downs JA, Allard S, Jobin-Robitaille O, Javaheri A, Auger A, Bouchard N, Kron SJ, Jackson SP, Cote J (2004) Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell 16 979-990... 

Sedelnikova OA, Pilch DR, Redon C, Bonner WM (2003) Histone H2AX in DNA damage and repair. Cancer Biol Ther 2 233-235... 

Ueda K, Kinoshita Y, Xu ZJ, Ide N, Ono M, Akahori Y, Tanaka I, Inoue M (2000) Unusual core histones specifically expressed in male gametic cells of Lilium longiflorum. Chromosoma 108 491—500 Unal E, Arbel-Eden A, Sattler U, Shroff R, Lichten M, Haber JE, Koshland D (2004) DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 16 991-1002... 

Sensing DNA damage is essential for maintenance of genomic integrity and cell cycle progression. DNA repair is the second major site of DNA synthesis in a cell after replication and it involves chromatin assembly after efficient repair process. In yeast, the histone chaperone CAF-1 (chromatin Assembly factorl) mediates histone H3-H4 assembly on to newly replicated DNA and also mediates nucleotide... 

Yaneva J, Leuba SH, van Holde K, Zlatanova J (1997) The major chromatin protein histone HI binds preferentially to cis-platinum-damaged DNA. Proc Natl Acad Sci USA 94(25) 13448-13451... 

Cell cycle progression, apoptosis, DNA damage and DNA repair are cellular functions that are regulated by several mechanisms. One such important regulatory mechanism is posttranslational modification of histone and non-histone proteins. Myriad of reports have been shown that acetylation of non-histone proteins apart from histones, contributes in major to these processes. 

Acetylation levels of histone and non-histone proteins are regulated upon DNA damage. Retinoblastoma protein pRb controls Gl-S phase transition and phosphorylation of pRb regulates it function. DNA damage induced acetylation of pRb near the phosphorylation sites prevents it phosphorylation and keep pRb in active form thereby leading to growth repression. DNA damage dependant association... 

Costanzo A, Merlo P, Pediconi N, Fulco M, Sartorelli V, Cole PA, Fontemaggi G, Fanciulli M, Schiltz L, Blandino G, Balsano C, Levrero M (2002) DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes. Mol Cell 9(1) 75-86 Davie JR, Hendzel MJ (1994) Multiple functions of dynamic histone acetylation. J Cell Biochem 55(1) ... 

Markham D, Munro S, Soloway J, O Connor DP, La Thangue NB (2006) DNA-damage-responsive acetylation of pRb regulates binding to E2F-1. EMBO Rep.7(2) 192-198 Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol. 6(11) 838-849... 

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). 

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