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Modeling genome-wide replication kinetics reveals a mechanism for regulation of replication timing.

Authors :
Yang, Scott Cheng‐Hsin
Rhind, Nicholas
Bechhoefer, John
Source :
Molecular Systems Biology. 2010, Vol. 6 Issue 1, p1-N.PAG. 13p. 7 Graphs.
Publication Year :
2010

Abstract

Microarrays are powerful tools to probe genome-wide replication kinetics. The rich data sets that result contain more information than has been extracted by current methods of analysis. In this paper, we present an analytical model that incorporates probabilistic initiation of origins and passive replication. Using the model, we performed least-squares fits to a set of recently published time course microarray data on Saccharomyces cerevisiae. We extracted the distribution of firing times for each origin and found that the later an origin fires on average, the greater the variation in firing times. To explain this trend, we propose a model where earlier-firing origins have more initiator complexes loaded and a more accessible chromatin environment. The model demonstrates how initiation can be stochastic and yet occur at defined times during S phase, without an explicit timing program. Furthermore, we hypothesize that the initiators in this model correspond to loaded minichromosome maintenance complexes. This model is the first to suggest a detailed, testable, biochemically plausible mechanism for the regulation of replication timing in eukaryotes. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17444292
Volume :
6
Issue :
1
Database :
Academic Search Index
Journal :
Molecular Systems Biology
Publication Type :
Academic Journal
Accession number :
131649746
Full Text :
https://doi.org/10.1038/msb.2010.61