Page last updated: 2024-10-24

histone H2AX kinase activity

Definition

Target type: molecularfunction

Catalysis of the transfer of a phosphate group to a histone variant H2AX. [GOC:bf]

Histone H2AX kinase activity is a critical function in the DNA damage response pathway. It involves the phosphorylation of histone H2AX, a core component of the nucleosome, at serine 139 (also known as γH2AX). This phosphorylation event is triggered by the detection of double-strand DNA breaks (DSBs), which are highly damaging lesions that can lead to genomic instability and cell death.

Upon DNA damage, various sensors and transducers activate the DNA damage response machinery. This includes the recruitment of the MRE11-RAD50-NBS1 (MRN) complex, which in turn activates ATM (ataxia telangiectasia mutated) kinase. ATM then phosphorylates a multitude of substrates, including H2AX.

The phosphorylation of H2AX serves as a signal for the recruitment of DNA repair machinery to the site of damage. γH2AX acts as a platform for the assembly of proteins involved in DSB repair, including checkpoint proteins, DNA repair enzymes, and chromatin remodelers. This assembly facilitates the initiation and execution of DNA repair mechanisms, such as homologous recombination (HR) and non-homologous end joining (NHEJ).

Furthermore, γH2AX plays a role in signaling DNA damage to other cellular processes, such as cell cycle arrest and apoptosis. This ensures that damaged cells are prevented from replicating their damaged DNA and that irreparable damage is eliminated.

Overall, histone H2AX kinase activity is an essential process in the DNA damage response pathway, crucial for maintaining genome integrity and protecting cells from the detrimental effects of DNA damage.'
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Proteins (1)

ProteinDefinitionTaxonomy
Serine/threonine-protein kinase VRK1A serine/threonine-protein kinase VRK1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99986]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
ro 31-8220Ro 31-8220: a protein kinase C inhibitorimidothiocarbamic ester;
indoles;
maleimides
EC 2.7.11.13 (protein kinase C) inhibitor
bi d1870