Histone H2AX

Histone H2AX is a variant histone protein that replaces conventional H2A in certain nucleosomes (UniProt: P16104). It plays a critical role in chromatin structure and accessibility, functioning in transcription regulation, DNA repair, DNA replication, and chromosomal stability. H2AX is particularly important for cell-cycle checkpoint control in response to ionizing radiation and for facilitating efficient repair of DNA double-strand breaks when phosphorylated at its C-terminus.

H2AX is a core component of the nucleosome and chromatin remodeling machinery, which is essential for all DNA-dependent cellular processes. The protein is ubiquitously expressed in human tissues given its fundamental role in DNA metabolism and genome maintenance.

In Alzheimer's Disease, H2AX is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of 1.069 across measured subcellular fractions in TMT-labeled, data-dependent acquisition proteomics of four subcellular compartments (P2, P3, S2, S3). This elevation may reflect increased DNA damage responses or altered chromatin dynamics in AD pathophysiology.