Mammalian histone acetyltransferase complexes

Over the last decade, great progress has been made in elucidating how the h uman genome operates in the chromatin context. This paper describes our wor k on two human acetyltransferases, PCAF and TIP60, and their interaction pa rtners. This study provides new clues on the function of these enzymes. In a striking parallel with the general transcription factor TFIID, PCAF compl ex contains proteins that have histone-like domains. We speculate that thes e subunits can presumably form a nucleosome-like structure on DNA, which wo uld allow PCAF to contribute to the maintenance of an active state of chrom atin. On the other hand, TIP60 complex contains two eukaryotic homologs of bacterial RuvB helicase/ATPse, involved in recombination and repair. Accord ingly, expression of a dominant negative mutant of TIP60 in living cells in terferes with their ability to repair DNA damage, which points out, for the first time, a role for a histone acetyltransferase in a process other than transcription. We also have evidence implicating TIP60 in the apoptotic re sponse to DNA damage.