histone H2AXY142 phosphatase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: histone H2AX tyrosine phosphate (position 142) + H2O = histone H2AX tyrosine (position 142) + phosphate. [PMID:19234442, PMID:19351884]

Histone H2AXY142 phosphatase activity refers to the enzymatic removal of a phosphate group from tyrosine 142 (Y142) of histone H2AX. This specific dephosphorylation event plays a crucial role in the DNA damage response (DDR) pathway, a cellular mechanism that ensures the proper repair of damaged DNA.

Histone H2AX is a variant of the core histone H2A that is ubiquitously expressed in eukaryotic cells. Upon DNA damage, H2AX undergoes phosphorylation at Y142 by kinases such as ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. This phosphorylation event, resulting in the formation of γH2AX, serves as a signal that attracts and recruits DDR proteins to the site of damage.

The dephosphorylation of γH2AX by histone H2AXY142 phosphatases is essential for the resolution of DNA damage and the restoration of normal chromatin structure. It effectively removes the signal that recruits DDR proteins, preventing excessive or prolonged signaling and allowing the damaged DNA to be repaired and the chromatin to return to its original state.

The specific molecular function of histone H2AXY142 phosphatase activity can be summarized as follows:

1. **Dephosphorylation of γH2AX**: The enzyme removes the phosphate group from Y142 of H2AX, converting γH2AX back to H2AX.

2. **Signal termination**: Dephosphorylation of γH2AX terminates the signaling cascade that recruits DDR proteins to the site of DNA damage.

3. **Chromatin restoration**: Removing the γH2AX signal allows for the restoration of normal chromatin structure and function.

4. **Regulation of DDR**: Histone H2AXY142 phosphatase activity plays a key role in regulating the duration and intensity of the DDR, ensuring that DNA repair occurs efficiently and that normal cellular processes are not disrupted.

The precise mechanism by which histone H2AXY142 phosphatases interact with γH2AX and remove the phosphate group is still under investigation. However, understanding the molecular function of this enzyme is crucial for gaining a complete picture of the intricate mechanisms that govern DNA repair and cellular responses to DNA damage.'
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Proteins (2)

Compounds (8)