H2AFX

From Wikipedia, the free encyclopedia

H2A histone family, member X

PDB rendering based on 1aoi.

Available structures: 1aoi, 1eqz, 1hio, 1hq3, 1kx3, 1kx4, 1kx5, 1s32, 1tzy, 2aro, 2cv5, 2f8n, 2hio, 2nzd

Identifiers

Symbol(s)

H2AFX; H2A.X; H2A/X; H2AX

External IDs

OMIM: 601772 MGI: 102688 HomoloGene: 68227

Gene ontology
Molecular Function:	• damaged DNA binding • protein binding
Cellular Component:	• nucleosome • nucleus • replication fork • chromosome
Biological Process:	• double-strand break repair via homologous recombination • DNA repair • DNA recombination • nucleosome assembly • chromosome organization and biogenesis (sensu Eukaryota) • cell cycle • meiosis • spermatogenesis

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_002105 (mRNA)
NP_002096 (protein)

NM_010436 (mRNA)
NP_034566 (protein)

Location

Chr 11: 118.47 - 118.47 Mb

Chr 9: 44.09 - 44.09 Mb

Pubmed search

[1]

[2]

H2AFX is one of several genes coding for histone H2A. In humans and other eukaryotes, the DNA is wrapped around histone-groups, consisting of core histones H2A, H2B, H3 and H4. Thus, the H2AFX contributes to the histone-formation and therefore the structure of DNA.

H2AX becomes phosphorylated on serine 139, then called gamma-H2AX, as a reaction on DNA Double-strand breaks (DSB). The kinases of the PIKK-family (Ataxia telangiectasia mutated, ATR and DNA-PKcs) are responsible for this phosphorylation, especially ATM. The modification can happen accidentally during replication fork collapse or in the response on ionizing radiation but also during controlled physiological processes such as V(D)J recombination. Gamma-H2AX is a sensitive target for looking at DSBs in cells. The role of the phosphorylated form of the histone in DNA repair is under discussion but it is known that because of the modification the DNA becomes less condensed. Delivering space for the recruitment of proteins necessary during repair of DSBs.

[edit] References

ncbi

[edit] Further reading

Redon C, Pilch D, Rogakou E, et al. (2002). "Histone H2A variants H2AX and H2AZ.". Curr. Opin. Genet. Dev. 12 (2): 162–9. PMID 11893489.
Fernandez-Capetillo O, Lee A, Nussenzweig M, Nussenzweig A (2005). "H2AX: the histone guardian of the genome.". DNA Repair (Amst.) 3 (8-9): 959–67. doi:10.1016/j.dnarep.2004.03.024. PMID 15279782.
Mannironi C, Bonner WM, Hatch CL (1990). "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.". Nucleic Acids Res. 17 (22): 9113–26. PMID 2587254.
Banerjee S, Smallwood A, Hultén M (1995). "ATP-dependent reorganization of human sperm nuclear chromatin.". J. Cell. Sci. 108 ( Pt 2): 755–65. PMID 7769017.
Ivanova VS, Hatch CL, Bonner WM (1994). "Characterization of the human histone H2A.X gene. Comparison of its promoter with other H2A gene promoters.". J. Biol. Chem. 269 (39): 24189–94. PMID 7929075.
Ivanova VS, Zimonjic D, Popescu N, Bonner WM (1994). "Chromosomal localization of the human histone H2A.X gene to 11q23.2-q23.3 by fluorescence in situ hybridization.". Hum. Genet. 94 (3): 303–6. PMID 8076949.
Rogakou EP, Pilch DR, Orr AH, et al. (1998). "DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.". J. Biol. Chem. 273 (10): 5858–68. PMID 9488723.
El Kharroubi A, Piras G, Zensen R, Martin MA (1998). "Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter.". Mol. Cell. Biol. 18 (5): 2535–44. PMID 9566873.
Rogakou EP, Boon C, Redon C, Bonner WM (1999). "Megabase chromatin domains involved in DNA double-strand breaks in vivo.". J. Cell Biol. 146 (5): 905–16. PMID 10477747.
Rogakou EP, Nieves-Neira W, Boon C, et al. (2000). "Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139.". J. Biol. Chem. 275 (13): 9390–5. PMID 10734083.
Paull TT, Rogakou EP, Yamazaki V, et al. (2001). "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.". Curr. Biol. 10 (15): 886–95. PMID 10959836.
Deng L, de la Fuente C, Fu P, et al. (2001). "Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones.". Virology 277 (2): 278–95. doi:10.1006/viro.2000.0593. PMID 11080476.
Chen HT, Bhandoola A, Difilippantonio MJ, et al. (2000). "Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX.". Science 290 (5498): 1962–5. PMID 11110662.
Chadwick BP, Willard HF (2001). "Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant.". Hum. Mol. Genet. 10 (10): 1101–13. PMID 11331621.
Burma S, Chen BP, Murphy M, et al. (2001). "ATM phosphorylates histone H2AX in response to DNA double-strand breaks.". J. Biol. Chem. 276 (45): 42462–7. doi:10.1074/jbc.C100466200. PMID 11571274.
Ward IM, Chen J (2002). "Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress.". J. Biol. Chem. 276 (51): 47759–62. doi:10.1074/jbc.C100569200. PMID 11673449.
Deng L, Wang D, de la Fuente C, et al. (2001). "Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA.". Virology 289 (2): 312–26. doi:10.1006/viro.2001.1129. PMID 11689053.
Chen A, Kleiman FE, Manley JL, et al. (2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase.". J. Biol. Chem. 277 (24): 22085–92. doi:10.1074/jbc.M201252200. PMID 11927591.
Zhu H, Hunter TC, Pan S, et al. (2003). "Residue-specific mass signatures for the efficient detection of protein modifications by mass spectrometry.". Anal. Chem. 74 (7): 1687–94. PMID 12033261.