H2AFX
Encyclopedia
H2AX is one of several gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s coding for histone H2A
Histone H2A
Histone H2A is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N terminal tail, H2A is involved with the structure of the nucleosomes of the 'beads on a string' structure.Other histone proteins...

. In humans and other eukaryotes, the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 is wrapped around histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...

-groups, consisting of core histones H2A, H2B, H3 and H4. Thus, the H2AX 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 PI3-family (Ataxia telangiectasia mutated
Ataxia telangiectasia mutated
Ataxia telangiectasia mutated is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis...

, ATR
Ataxia telangiectasia and Rad3 related
Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein or FRAP-related protein 1 is an enzyme that in humans is encoded by the ATR gene...

 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. Delivering 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
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with MDC1
MDC1
Mediator of DNA damage checkpoint protein 1 is a protein that in humans is encoded by the MDC1 gene.-Interactions:MDC1 has been shown to interact with MRE11A, H2AFX and CHEK2.-Further reading:...

, Nibrin
Nibrin
Nibrin, also known as NBN, is a protein which in humans is encoded by the NBN gene.- Function :Nibrin is a protein associated with the repair of double strand breaks which pose serious damage to a genome. It is a 754 amino acid protein identified as a member of the NBS1/hMre11/RAD50 double strand...

, TP53BP1
TP53BP1
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.- Clinical significance :53BP1 is underexpressed in most cases of triple-negative breast cancer....

, Bloom syndrome protein
Bloom syndrome protein
Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is expressed in Bloom syndrome.The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities...

, BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...

 and BARD1
BARD1
BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.-Interactions:BARD1 has been shown to interact with BRE, UBE2D1, CSTF2, BRCC3, RAD51, BCL3, TACC1, Ewing sarcoma breakpoint region 1, FANCD2, H2AFX, CSTF1, NPM1, BRCA2, BRCA1, P53 and Aurora B...

.

Further reading

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK