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Mathematical modelling of whole chromosome replication

By Alessandro P.S. de Moura, Renata Retkute, Michelle Hawkins and Conrad A. Nieduszynski


All chromosomes must be completely replicated prior to cell division, a requirement that demands the activation of a sufficient number of appropriately distributed DNA replication origins. Here we investigate how the activity of multiple origins on each chromosome is coordinated to ensure successful replication. We present a stochastic model for whole chromosome replication where the dynamics are based upon the parameters of individual origins. Using this model we demonstrate that mean replication time at any given chromosome position is determined collectively by the parameters of all origins. Combining parameter estimation with extensive simulations we show that there is a range of model parameters consistent with mean replication data, emphasising the need for caution in interpreting such data. In contrast, the replicated-fraction at time points through S phase contains more information than mean replication time data and allowed us to use our model to uniquely estimate many origin parameters. These estimated parameters enable us to make a number of predictions that showed agreement with independent experimental data, confirming that our model has predictive power. In summary, we demonstrate that a stochastic model can recapitulate experimental observations, including those that might be interpreted as deterministic such as ordered origin activation times

Publisher: Oxford Journals
Year: 2010
OAI identifier:
Provided by: Nottingham ePrints

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  21. (1979). High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules.
  22. (2008). How Xenopus laevis embryos replicate reliably: investigating the random-completion problem.
  23. (2000). Is there replication-associated mutational pressure in the Saccharomyces cerevisiae genome?
  24. (2002). Ku complex controls the replication time of DNA in telomere regions. doi
  25. (2006). Live-cell imaging reveals replication of individual replicons in eukaryotic replication factories.
  26. (1993). Location and characterization of autonomously replicating sequences from chromosome VI of Saccharomyces cerevisiae.
  27. (2002). Mapping of early firing origins on a replication profile of budding yeast.
  28. (1968). On the mechanism of DNA replication in mammalian chromosomes.
  29. (2007). OriDB: a DNA replication origin database.
  30. (2005). Origin recognition and the chromosome cycle.
  31. (2004). Regulation of early events in chromosome replication.
  32. (2001). Replication dynamics of the yeast genome.
  33. (2007). Replication in hydroxyurea: it’s a matter of time.
  34. (1980). Replication of small chromosomal DNAs in yeast.
  35. (1997). Replication profile of Saccharomyces cerevisiae chromosome VI. Genes to Cells,
  36. (2008). Stochastic hybrid modeling of DNA replication across a complete genome.
  37. (2009). Stochastic modelling for quantitative description of heterogeneous biological systems.
  38. (2008). The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae.
  39. (1997). The efficiency and timing of initiation of replication of multiple replicons of Saccharomyces cerevisiae chromosome VI.
  40. (2009). The origin recognition complex interacts with a subset of metabolic genes tightly linked to origins of replication.
  41. (2005). The requirement of yeast replication origins for pre-replication complex proteins is modulated by transcription.
  42. (2008). The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.
  43. (2009). Universal temporal profile of replication origin activation in eukaryotes.
  44. (2004). Yeast as a touchstone in post-genomic research: strategies for integrative analysis in functional genomics.

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