A mathematical model of CENP-A incorporation in mammalian centromeres.
Centromere Protein A (CENP-A) is a histone H3 variant found at mammalian centromeres. Unlike canonical histones which are incorporated at centromeres in S phase, CENP-A is deposited at centromeric chromatin in G1. Although recent studies have elucidated many of the molecular details associated with the CENP-A incorporation pathway, some aspects of the process are still not fully understood. CENP-A incorporation in G1 requires multiple assembly factors for its recruitment and maintenance. In this study, the first mathematical model of the CENP-A incorporation pathway is developed. The model is based on what is currently known about the pathway and is calibrated by comparing numerical simulations with experimental observations taken from the literature. The model succinctly collates a large body of knowledge accumulated in recent decades concerning the pathway and produces results that are consistent with experimental findings. It identifies possible gaps in what is currently known about the pathway and suggests possible directions for future research. It is envisaged that the model will be expanded upon and improved as more information concerning the pathway comes to light.
School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, University Road, Galway, Ireland. Electronic address: kevindoherty1984@gmail.com.
Kevin
K
Doherty
School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, University Road, Galway, Ireland. Electronic address: martin.meere@nuigalway.ie.
Martin
M
Meere
School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, University Road, Galway, Ireland. Electronic address: petri.piiroinen@nuigalway.ie.
Petri T
PT
Piiroinen
D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D059447:Cell Cycle Checkpoints; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000378:metabolism; D016193:G1 Phase; D020690:GTPase-Activating Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007700:Kinetics; D055641:Mathematical Concepts; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D049490:Systems Biology
D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; C524371:HJURP protein, human; C115995:mgcRacGAP
CENP-A; Centromere; Histone; Mathematical modelling; Nucleosome