A breaking strategy for topoisomerase IIβ/PARP-1-dependent regulated transcription

While diverse enzymatic activities are required for transcriptional initiation, a central question remains whether additional enzymatic activities involved in other cellular processes may also be critical for regulated gene activation. Recently, we reported that signal-dependent activation of gene transcription requires topoisomerase II beta ( Topo II beta)-dependent, nucleosome-specific, transient double-stranded DNA break formation with subsequent activation of poly( ADP-ribose) polymerase-1 (PARP-1) enzymatic function, which causes local changes of chromatin architecture (Ju et al., Science 2006; 312: 1798-802). Here, we discussed that possible molecular mechanism underling Topo II beta/PARP-1/DNA-PK network in transcriptional initiation and many intriguing issues remain to be solved in the future.