H2ax

H2AX is a variant of the histone H2A family, which plays a critical role in the cellular response to DNA damage. It is encoded by the H2AFX gene in humans. H2AX is involved in the maintenance of genomic stability and is a key player in the DNA damage response (DDR) pathway.

Structure

H2AX is a member of the histone H2A family, which are proteins that package and order DNA into structural units called nucleosomes. The H2AX protein is similar in structure to other H2A histones but contains a unique C-terminal tail that is crucial for its function in DNA repair.

Function

H2AX is primarily known for its role in the cellular response to double-strand breaks (DSBs) in DNA. Upon the occurrence of DSBs, H2AX is rapidly phosphorylated at a serine residue (Ser139) near its C-terminus. This phosphorylated form of H2AX is known as γ-H2AX.

Phosphorylation and γ-H2AX

The phosphorylation of H2AX to form γ-H2AX is one of the earliest events in the DNA damage response. This modification is catalyzed by members of the PI3K-related protein kinase family, including ATM, ATR, and DNA-PKcs. γ-H2AX serves as a marker for DNA damage and facilitates the recruitment of DNA repair proteins to the site of damage.

Role in DNA Repair

γ-H2AX plays a crucial role in the recruitment and retention of DNA repair proteins at the site of damage. It acts as a platform for the assembly of repair complexes, including the MRN complex (MRE11-RAD50-NBS1) and other factors involved in homologous recombination and non-homologous end joining.

Clinical Significance

The presence of γ-H2AX foci is used as a biomarker for DNA damage in various clinical and research settings. Elevated levels of γ-H2AX are associated with increased genomic instability and have been observed in cancer cells. The detection of γ-H2AX is also used to assess the efficacy of radiotherapy and chemotherapy in inducing DNA damage in cancer cells.

Research Applications

H2AX and γ-H2AX are widely used in research to study the mechanisms of DNA repair and the cellular response to DNA damage. The formation of γ-H2AX foci can be visualized using immunofluorescence microscopy, providing insights into the dynamics of DNA repair processes.

See Also

• Histone
• DNA damage response
• Double-strand break
• ATM serine/threonine kinase
• ATR serine/threonine kinase
• DNA-PKcs

External Links

• [H2AX entry in UniProt]
• [H2AFX gene information in NCBI]