QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 1, 308-316, January 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-07-0657v1 17/1/308    most recent Alert me when this article is cited Alert me if a correction is posted 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 Patel, P. K. Articles by Rhind, N. Search for Related Content PubMed PubMed Citation Articles by Patel, P. K. Articles by Rhind, N.

DNA Replication Origins Fire Stochastically in Fission Yeast

Prasanta K. Patel ^*, Benoit Arcangioli , Stephen P. Baker , Aaron Bensimon , and Nicholas Rhind ^*

^* Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605; Department of Information Services, University of Massachusetts Medical School, Worcester, MA 01605; Genome Dynamics Unit, Pasteur Institute, 75724 Paris, France; and Genomes Stability Unit, Pasteur Institute, 75724 Paris, France

Submitted July 20, 2005; Revised October 14, 2005; Accepted October 18, 2005
Monitoring Editor: Mark Solomon

DNA replication initiates at discrete origins along eukaryotic chromosomes. However, in most organisms, origin firing is not efficient; a specific origin will fire in some but not all cell cycles. This observation raises the question of how individual origins are selected to fire and whether origin firing is globally coordinated to ensure an even distribution of replication initiation across the genome. We have addressed these questions by determining the location of firing origins on individual fission yeast DNA molecules using DNA combing. We show that the firing of replication origins is stochastic, leading to a random distribution of replication initiation. Furthermore, origin firing is independent between cell cycles; there is no epigenetic mechanism causing an origin that fires in one cell cycle to preferentially fire in the next. Thus, the fission yeast strategy for the initiation of replication is different from models of eukaryotic replication that propose coordinated origin firing.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Nicholas Rhind (nick.rhind{at}umassmed.edu).

This article has been cited by other articles:

				J. Lygeros, K. Koutroumpas, S. Dimopoulos, I. Legouras, P. Kouretas, C. Heichinger, P. Nurse, and Z. Lygerou Stochastic hybrid modeling of DNA replication across a complete genome PNAS, August 26, 2008; 105(34): 12295 - 12300. [Abstract] [Full Text] [PDF]

				M. L. Hoang, R. P. Leon, L. Pessoa-Brandao, S. Hunt, M. K. Raghuraman, W. L. Fangman, B. J. Brewer, and R. A. Sclafani Structural Changes in Mcm5 Protein Bypass Cdc7-Dbf4 Function and Reduce Replication Origin Efficiency in Saccharomyces cerevisiae Mol. Cell. Biol., November 1, 2007; 27(21): 7594 - 7602. [Abstract] [Full Text] [PDF]

				M. Benard, C. Maric, and G. Pierron Low rate of replication fork progression lengthens the replication timing of a locus containing an early firing origin Nucleic Acids Res., September 27, 2007; 35(17): 5763 - 5774. [Abstract] [Full Text] [PDF]

				C. Speck and B. Stillman Cdc6 ATPase Activity Regulates ORC{middle dot}Cdc6 Stability and the Selection of Specific DNA Sequences as Origins of DNA Replication J. Biol. Chem., April 20, 2007; 282(16): 11705 - 11714. [Abstract] [Full Text] [PDF]