A breaking strategy for topoisomerase IIbeta/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 IIbeta (Topo IIbeta)-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 IIbeta/PARP-1/DNA-PK network in transcriptional initiation and many intriguing issues remain to be solved in the future.
Ju
Bong-Gun
BG
Howard Hughes Medical Institute, Department of Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, California 92093-0648, USA.
Rosenfeld
Michael G
MG
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D000072200:Ku Autoantigen; D008954:Models, Biological; D015530:Nuclear Matrix / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002843:Chromatin; D004268:DNA-Binding Proteins; D011065:Poly(ADP-ribose) Polymerases; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen; D004250:DNA Topoisomerases, Type II