HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dimitrova, D. S. Search for Related Content PubMed PubMed Citation Articles by Dimitrova, D. S.

Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA

I have demonstrated that nuclear transcription modulates the distribution of replication origins along mammalian chromosomes. Chinese Hamster Ovary (CHO) cells were exposed to transcription inhibitors in early G1 phase and replication origin sites in the dihydrofolate reductase (DHFR) gene locus were mapped several hours later. DNA within nuclei prepared from control and transcription-deficient G1-phase cells was replicated with similar efficiencies when introduced into Xenopus egg extracts. Replication initiated in the intergenic region within control late-G1 nuclei, but randomly within transcriptionally repressed nuclei. Random initiation was not a consequence of inability to produce an essential protein(s), since initiation was site-specific within cells exposed to the translation inhibitor cycloheximide during the same interval of G1 phase. Furthermore, in vivo inhibition of transcription within late-G1-phase cells reduced the frequency of usage of pre-established DHFR replication origin sites. Transcription rates in the DHFR domain were very low and did not change throughout G1 phase. This implies that, although ongoing nuclear transcription is required, local expression of the genes in the DHFR locus alone is not sufficient to create a site-specific replication initiation pattern. I conclude that epigenetic factors, including general nuclear transcription, play a role in replication origin selection in mammalian nuclei.

^aPresent address: The Babraham Institute, Cambridge, CB2 4AT UK

^* Correspondence: E-mail: daniela.dimitrova{at}bbsrc.ac.uk

This article has been cited by other articles:

				A. J. Murray Pharmacological PKA Inhibition: All May Not Be What It Seems Sci. Signal., June 3, 2008; 1(22): re4 - re4. [Abstract] [Full Text] [PDF]

				L. Szekvolgyi, Z. Rakosy, B. L. Balint, E. Kokai, L. Imre, G. Vereb, Z. Bacso, K. Goda, S. Varga, M. Balazs, et al. Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA PNAS, September 18, 2007; 104(38): 14964 - 14969. [Abstract] [Full Text] [PDF]