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'''H2AFX''' (H2A histone family, member X) is one of several [[gene]]s 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 H2AX contributes to the nucleosome-formation and therefore the structure of DNA.
'''H2AFX''' (H2A histone family, member X) is one of several [[gene]]s 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 H2AX contributes to the nucleosome-formation and therefore the structure of DNA.


H2AX becomes phosphorylated on serine 139, then called gamma-H2AX, as a reaction on [[DNA repair#Double-strand breaks|DNA Double-strand breaks (DSB)]]. The kinases of the PI3-family ([[Ataxia telangiectasia mutated]], [[Ataxia telangiectasia and Rad3 related|ATR]] and DNA-PKcs) are responsible for this phosphorylation, especially ATM. The modification can happen accidentally during replication fork collapse or in the response to 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, potentially allowing space for the recruitment of proteins necessary during repair of DSBs. Mutagenesis experiments have shown that the modification is necessary for the proper formation of ionizing radiation induced foci in response to double strand breaks, but is not required for the recruitment of proteins to the site of DSBs.
H2AX becomes phosphorylated on serine 139, then called gamma-H2AX, as a reaction on [[DNA repair#Double-strand breaks|DNA Double-strand breaks (DSB)]]. The kinases of the PI3-family ([[Ataxia telangiectasia mutated]], [[Ataxia telangiectasia and Rad3 related|ATR]] and DNA-PKcs) are responsible for this phosphorylation, especially ATM. The modification can happen accidentally during replication fork collapse or in the response to 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 presence of gamma-H2AX by itsels, hovwever, is not the evidence of the DSBs <ref>Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks. Rybak P, Hoang A, Bujnowicz L, Bernas T, Berniak K, Zarębski M, Darzynkiewicz Z, Dobrucki J.
Oncotarget. 7:49574-49587. PMID: 2739133. </ref>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, potentially allowing space for the recruitment of proteins necessary during repair of DSBs. Mutagenesis experiments have shown that the modification is necessary for the proper formation of ionizing radiation induced foci in response to double strand breaks, but is not required for the recruitment of proteins to the site of DSBs.


== Interactions ==
== Interactions ==

Revision as of 23:49, 11 November 2017

H2AFX (H2A histone family, member X) 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 H2AX contributes to the nucleosome-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 PI3-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 to 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 presence of gamma-H2AX by itsels, hovwever, is not the evidence of the DSBs [1]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, potentially allowing space for the recruitment of proteins necessary during repair of DSBs. Mutagenesis experiments have shown that the modification is necessary for the proper formation of ionizing radiation induced foci in response to double strand breaks, but is not required for the recruitment of proteins to the site of DSBs.

Interactions

H2AX has been shown to interact with:

References

  1. ^ Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks. Rybak P, Hoang A, Bujnowicz L, Bernas T, Berniak K, Zarębski M, Darzynkiewicz Z, Dobrucki J. Oncotarget. 7:49574-49587. PMID: 2739133.
  2. ^ a b Mallery DL, Vandenberg CJ, Hiom K (Dec 2002). "Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains". The EMBO Journal. 21 (24): 6755–62. doi:10.1093/emboj/cdf691. PMC 139111. PMID 12485996.
  3. ^ a b Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ (Jun 2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase". The Journal of Biological Chemistry. 277 (24): 22085–92. doi:10.1074/jbc.M201252200. PMID 11927591.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM. "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage". Current Biology. 10 (15): 886–95. doi:10.1016/s0960-9822(00)00610-2. PMID 10959836.
  5. ^ a b Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC (Sep 2004). "Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest". The Journal of Cell Biology. 166 (6): 801–13. doi:10.1083/jcb.200405128. PMC 2172115. PMID 15364958.
  6. ^ Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (Feb 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". Nature. 421 (6926): 961–6. doi:10.1038/nature01446. PMID 12607005.
  7. ^ Xu X, Stern DF (Oct 2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB Journal. 17 (13): 1842–8. doi:10.1096/fj.03-0310com. PMID 14519663.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Kobayashi J, Tauchi H, Sakamoto S, Nakamura A, Morishima K, Matsuura S, Kobayashi T, Tamai K, Tanimoto K, Komatsu K (Oct 2002). "NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain". Current Biology. 12 (21): 1846–51. doi:10.1016/s0960-9822(02)01259-9. PMID 12419185.
  9. ^ Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, Carpenter PB, Bonner WM, Chen J, Nussenzweig A (Dec 2002). "DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1". Nature Cell Biology. 4 (12): 993–7. doi:10.1038/ncb884. PMID 12447390.
  10. ^ Ward IM, Minn K, Jorda KG, Chen J (May 2003). "Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX". The Journal of Biological Chemistry. 278 (22): 19579–82. doi:10.1074/jbc.C300117200. PMID 12697768.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Further reading

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