title: Co-mutation of histone H2AX S139A with Y142A rescues Y142A-induced ionising radiation sensitivity.
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.
authors.affiliation: Genome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: James A L
authors.initials: JA
authors.lastname: Brown
authors.forename: John K
authors.initials: JK
authors.lastname: Eykelenboom
authors.forename: Noel F
authors.initials: NF
authors.lastname: Lowndes
keywords: 53BP1; A, alanine; DSB; DSB, DNA double strand break; F, phenylalanine; Fig, Figure; H2AX; H2AX/H2ax, MDC1/Mdc1, RAD51/Rad51 and 53BP1/53Bp1, indicate human or mouse/chicken proteins respectively; IR; IR, ionising radiation; IRIF, ionising radiation induced foci; RT-PCR, reverse transcription polymerase chain reaction; S139; W, tryptophan; WSTF, Williams–Beuren syndrome transcription factor kinase; WT, Wild type; Y, tyrosine; Y142