Laboratory of Computational Proteomics
Research: Modeling and Simulation of biological systems
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Center for Health Informatics and Bioinformatics
 
High Performance Computing Facility
NYU Langone Medical Center
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Modeling of replication fork progression throughout the yeast genome

We assayed replication dynamics using whole genome time-resolved chromatin immunoprecipitation combined with microarray analysis of the GINS complex, an integral member of the replication fork. The data show that the replication fork progresses at highly uniform rates regardless of genomic location, revealing that replication fork dynamics in yeast is simpler and more uniform than previously envisaged. We developed a parsimonious model to accurately simulate fork movement throughout the genome. Our model uses a parsimonious set of assumptions: (1) the firing time of a given origin in a population of cells is normally distributed with a mean firing time specific to the origin; (2) the standard deviation of the firing times is constant for all origins in each simulated region; (3) the velocity of progression is the same for all forks (v=1.6 kb/min); and (4) GINS fall off the chromosomes when adjacent forks collide.

Figure S-phase time-course data (experiment left and simulations right) for several genomic regions of interest. (A) ChrVIII coordinates 240370 kb. A category 1 origin flanked by two category 2 origins. (B) Seven category 1 origins spaced unevenly between 320 and 600 kb of ChrIV. (C) ChrXII coordinates 510600 kb. The gap in between the two noted origins is 97 kb, among the longest inter-origin distances observed in the yeast genome. (D) The right-hand telomeric region of ChrXIII. The telomeric region is shaded. (E) The centromeric region of ChrIX (shaded gray). (F) A category 3 origin (shaded gray) located at B695 kb (ARS1625) in ChrXVI.

Reference

  • M.D. Sekedat, D. Fenyö, R.S. Rogers, A.J. Tackett, J.D. Aitchison, B.T. Chait, "GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome", Mol Syst Biol. 6 (2010) 353.

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