Histone H2AX

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Histone H2AX
Properties of human protein
Mass / length primary structure 142 amino acids
Secondary to quaternary structure H2A-H2B heterodimer
Identifier
Gene name H2AFX
External IDs
Occurrence
Parent taxon Eukaryotes

gH2AX foci in a mouse cell. The gH2AX foci can be seen in green, the DNA of the cell nucleus was stained with DAPI (blue)

The histone H2AX is a protein from the group of histones that occurs in the nucleus of all eukaryotes . It stabilizes the genetic information ( DNA ) and, together with the DNA molecules, forms nucleosomes and chromatin complexes with other proteins . In addition, H2AX has multiple roles in DNA repair , chromosome maintenance and the cell cycle . H2AX also has medical significance as a laboratory value for DNA damage.

Localization

It is a variant of the histone H2A and is therefore an essential component of chromatin . In eukaryotic cells, the DNA is wound around a histone octamer, which consists of the histones H2A , H2B , H3 and H4 . In around 20% of all histone octamers, H2A has been replaced by H2AX.

function

DNA repair

As a reaction to a DNA double-strand break , for example , H2AX is phosphorylated at serine 139; the phosphorylated form of H2AX is called gamma-H2AX (abbreviated as gH2AX or yH2AX). Kinases from the family of PI3 kinases ( ATM , ATR and DNA-PKcs) are responsible for the phosphorylation . gH2AX is formed in an area of ​​approx. 1-2 mega base pairs around the double-strand break and is thus visible as a focus in the microscope after immunofluorescence staining . The formation of gH2AX also takes place without exposure to exogenous noxae such as ionizing radiation during V (D) J recombination or during the replication of the DNA when replication forks collapse. Gamma-H2AX has established itself as sensitive detection for DNA double strand breaks in science, especially in radiation biology . The biological function of gH2AX is not yet fully understood. Investigations with cells lacking H2AX showed that the repair of radiation-induced DNA double-strand breaks is only possible to a limited extent.

Interactions with other proteins

H2AX interacts with MDC1 , Nibrin , TP53BP1 , BRCA1 and BARD1, among others .

literature

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  • Mannironi C, Bonn WM, Hatch CL: H2A.X. A histone isoprotein with a conserved C-terminal sequence, is encoded by a novel mRNA with both DNA replication type and polyA 3 'processing signals . In: Nucleic Acids Res . 17, No. 22, 1990, pp. 9113-26. doi : 10.1093 / nar / 17.22.9113 . PMID 2587254 . PMC 335118 (free full text).
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  • Ivanova VS, Hatch CL, Bonner WM: Characterization of the human histone H2A.X gene. Comparison of its promoter with other H2A gene promoters . In: J. Biol. Chem. . 269, No. 39, 1994, pp. 24189-94. PMID 7929075 .
  • Ivanova VS, Zimonjic D, Popescu N, Bonner WM: Chromosomal localization of the human histone H2A.X gene to 11q23.2-q23.3 by fluorescence in situ hybridization . In: Hum. Genet. . 94, No. 3, 1994, pp. 303-6. doi : 10.1007 / BF00208289 . PMID 8076949 .
  • Rogakou EP, Pilch DR, Orr AH, et al. : DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 . In: J. Biol. Chem. . 273, No. 10, 1998, pp. 5858-68. doi : 10.1074 / jbc.273.10.5858 . PMID 9488723 .
  • El Kharroubi A, Piras G, Zensen R, Martin MA: Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter . In: Mol. Cell. Biol . 18, No. 5, 1998, pp. 2535-44. PMID 9566873 . PMC 110633 (free full text).
  • Rogakou EP, Boon C, Redon C, Bonner WM: Megabase chromatin domains involved in DNA double-strand breaks in vivo . In: J. Cell Biol. . 146, No. 5, 1999, pp. 905-16. doi : 10.1083 / jcb.146.5.905 . PMID 10477747 . PMC 2169482 (free full text).
  • Rogakou EP, Nieves-Neira W, Boon C, et al. : Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139 . In: J. Biol. Chem. . 275, No. 13, 2000, pp. 9390-5. doi : 10.1074 / jbc.275.13.9390 . PMID 10734083 .
  • Paull TT, Rogakou EP, Yamazaki V, et al. : A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage . In: Curr. Biol . 10, No. 15, 2001, pp. 886-95. doi : 10.1016 / S0960-9822 (00) 00610-2 . PMID 10959836 .
  • Deng L, de la Fuente C, Fu P, et al. : Acetylation of HIV-1 Tat by CBP / P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones . In: Virology . 277, No. 2, 2001, pp. 278-95. doi : 10.1006 / viro.2000.0593 . PMID 11080476 .
  • Chen HT, Bhandoola A, Difilippantonio MJ, et al. : Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX . In: Science . 290, No. 5498, 2000, pp. 1962-5. doi : 10.1126 / science.290.5498.1962 . PMID 11110662 .
  • Chadwick BP, Willard HF: Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant . In: Hum. Mol. Genet. . 10, No. 10, 2001, pp. 1101-13. doi : 10.1093 / hmg / 10.10.1101 . PMID 11331621 .
  • Burma S, Chen BP, Murphy M, et al. : ATM phosphorylates histone H2AX in response to DNA double-strand breaks . In: J. Biol. Chem. . 276, No. 45, 2001, pp. 42462-7. doi : 10.1074 / jbc.C100466200 . PMID 11571274 .
  • Ward IM, Chen J: Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress . In: J. Biol. Chem. . 276, No. 51, 2002, pp. 47759-62. PMID 11673449 .
  • Deng L, Wang D, de la Fuente C, et al. : Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA . In: Virology . 289, No. 2, 2001, pp. 312-26. doi : 10.1006 / viro.2001.1129 . PMID 11689053 .
  • Chen A, Kleiman FE, Manley JL, et al. : Autoubiquitination of the BRCA1 * BARD1 RING ubiquitin ligase . In: J. Biol. Chem. . 277, No. 24, 2002, pp. 22085-92. doi : 10.1074 / jbc.M201252200 . PMID 11927591 .
  • Zhu H, Hunter TC, Pan S, et al. : Residue-specific mass signatures for the efficient detection of protein modifications by mass spectrometry . In: Anal. Chem. . 74, No. 7, 2003, pp. 1687-94. doi : 10.1021 / ac010853p . PMID 12033261 .

Individual evidence

  1. ↑ Search result UniProt H2A family
  2. ↑ UniProt P16104