Abstract
Under normal conditions histone H2AX is constitutively phosphorylated on tyrosine (Y) 142 by Williams–Beuren syndrome transcription factor kinase (WSTF). Following DNA double strand breaks (DSB), Y142 is de‐phosphorylated and serine (S) 139 is phosphorylated. Here we explored DSB‐dependent cross talk between H2AX residues S139 and Y142. H2axY142A mutation resulted in increased sensitivity to ionising radiation (IR), compared to H2axS139A. Interestingly, co‐mutation of S139A and Y142A rescued IR sensitivity. The DSB response proteins 53Bp1 and Rad51 were recruited to IR‐induced foci (IRIF) in H2axS139A, H2axY142A and H2axS139A/Y142A cells. Our results suggest that H2axY142A IR sensitivity is dependent upon the C‐terminal residue, S139.