Lack of effect of RuvB-like proteins on DNA damage signaling activation.
Ataxia telangiectasia mutated (ATM) kinase is a central player in cellular response to DNA damage. Phosphorylation of the histone H2AX by ATM is required for the accumulation of repair proteins at the sites of double-strand breaks. Recently, it was reported that the histone acetyltransferase Tat interactive protein-60 (IPP60) is required to acetylate ATM prior to its activation. The RuvB-like proteins TIP48 and TIP49 are known to be necessary for the assembly and functional activity of the TIP60 acetyltransferase complex. In the present communication, we investigated the requirements of IIP48 and IIP49 for ATM activation by monitoring the cell cycle distribution and H2AX phosphorylation after irradiation of IIP48- and IIP49-depleted cells. We found that neither the cell cycle norgammay-H2AX were affected in IIP48- and IIP49-silenced cells, suggesting that the IIP60 chromatin modification complex is not engaged in DNA damage signaling upstream of ATM.
Gospodinov
Anastas
A
Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad G. Bonchev Str. 21, Sofia 1113, Bulgaria. agg@bio21.bas.bg
Anachkova
Boyka
B
D000074183:ATPases Associated with Diverse Cellular Activities; D001426:Bacterial Proteins / Q000494:pharmacology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects*; D004265:DNA Helicases / Q000494:pharmacology; D017931:DNA Primers; D020868:Gene Silencing; D051548:Histone Acetyltransferases / Q000494:pharmacology; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008297:Male; D011471:Prostatic Neoplasms; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D001426:Bacterial Proteins; D002352:Carrier Proteins; D017931:DNA Primers; C061260:RuvB protein, Bacteria; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human; C122079:RUVBL2 protein, human