H2AFX
Human Histone H2A Family Member X (H2AFX)
Description
H2AFX is a variant of histone H2A, a core component of nucleosomes, the basic units of chromatin packaging in eukaryotic cells. Nucleosomes are composed of an octamer of histones (two copies each of H2A, H2B, H3, and H4) around which approximately 147 base pairs of DNA are wrapped. Histones play critical roles in regulating gene expression, DNA replication, and DNA repair.
H2AFX is distinguished from its canonical counterpart, H2A, by the presence of a conserved serine residue at position 139, known as the S139 residue. This residue is a target for phosphorylation by a family of kinases known as phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including ATM, ATR, and DNA-PK. Phosphorylation of S139 creates the γH2AX variant, often referred to as a hallmark of DNA damage.
Associated Diseases
Mutations or alterations in H2AFX have been associated with several diseases, including:
- Breast cancer: H2AFX mutations have been linked to an increased risk of breast cancer, particularly in women with a family history of the disease.
- Ovarian cancer: H2AFX mutations are found in approximately 10% of ovarian cancers.
- Other cancers: H2AFX mutations have also been observed in other types of cancer, including lung cancer, colorectal cancer, and melanoma.
- Neurological disorders: Mutations in H2AFX have been implicated in certain neurological disorders, such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
- Immunodeficiency disorders: Rare mutations in H2AFX can result in immunodeficiency disorders characterized by recurrent infections.
Did you Know ?
- Phosphorylated γH2AX can be detected in the vicinity of DNA damage sites within minutes of the damage occurring. This rapid response highlights the critical role of H2AFX in coordinating the cellular response to DNA breaks.
