کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1981877 | 1539422 | 2012 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Co-mutation of histone H2AX S139A with Y142A rescues Y142A-induced ionising radiation sensitivity Co-mutation of histone H2AX S139A with Y142A rescues Y142A-induced ionising radiation sensitivity](/preview/png/1981877.png)
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.
▸ H2AX-Y142A cells display a slow growth phenotype. ▸ We report H2AX-Y142A cells have increased constitutive cell death. ▸ We found that cells expressing H2AX-Y142A are IR sensitive. ▸ Combining H2AX mutations Y142A and S139A rescues the Y142A IR sensitivity. ▸ H2AX-Y142A cells can recruit the DNA repair proteins 53BP1 and Rad51.
Journal: FEBS Open Bio - Volume 2, 2012, Pages 313–317