报告题目：Emergence of the spatio-temporal DNA replication program: Role of origin distribution heterogeneity and 3D chromatin structures
主持人：张三军研究员
时间：12月4日（周二）下午1:30
地点：理科大楼A814会议室
主办单位：精密光谱科学与技术国家重点实验室
报告摘要：
We recently proposed a simple model with natural hypothesis that reproduces the time dependence of DNA replication kinetics (Arbona 2018). In this model, fork-component recycling and potential replication origins (p-ori) localization are sufficient spatial ingredients to explain that the frequency of new replication origin firing per length of unreplicated DNA along the S-phase, I(t), presents a universal bell shape in eukaryotes (Goldar, 2009). Our model predicts that the maximum value for I(t) is intimately related to the density of p-oris and the replication speed. Without free parameter, this relationship holds for 5 species with up to a 300 fold difference of Imax (Arbona 2018).
We will first review how this model captures the time dependence of DNA replication dynamics. In a second step, we will present results from spatio-temporal DNA replication program simulations of our model based on p-ori distributions with heterogeneities in origins’ strength and spatial distributions. These distributions are drawn from chromatin mark profiles that have been associated to replication initiation (e.g. DNase I sensitivity, Gindin 2014). Comparison with low resolution (~100 kb, mean replication timing, MRT) and recent high resolution (~5 kb, replication fork directionality, Petryk 2015) experimental profiling of the replication program provides original information about the mechanisms underlying replication origins specification (number, positioning and strength) in higher eukaryotes. Finally, we will discuss preliminary data obtained by 3D molecular dynamics simulations of our model where chromosomes are confined in a spherical nucleus and, firing factors are free to diffuse and to bind to proximal p-oris to initiate replication.
报告人简介：
October 2014 Director of Research at Centre National de la Recherche Scientifique (CNRS).
November 2012 Diploma of “Habilitation `a diriger des Recherches” (HDR, accreditation to supervise research) (ENS de Lyon) : Multi-scale analysis of the mammalian replication programme.
November 2003 Research Associate at Centre National de la Recherche Scientifique (CNRS).
Research unit: Laboratoire de Physique of ENS-Lyon (UMR5672). Associated to Laboratoire Joliot-Curie in 2003–2010 and member of LJC resident team during 2011.
2000-2003 Post-doctorate at the European Bioinformatics Institute (EMBL-EBI) (Christos Ouzounis, Computational Genomics Group).
Marie Curie fellowship for the project: Global measures for genome structure and evolution (2001-2003).
1996-2000 PhD Thesis: “Statistical analysis of DNA sequences using the wavelet transform”.
Supervisor: Prof. Alain Arneodo.
Centre de Recherche Paul Pascal, University of Bordeaux, France.
1994-1995 Diplome d’ Etude Approfondie (Champs Particules Matieres), University of Paris VI. Equivalent to a Master of Science.
1992-1995 Diplome de l’ Ecole Superieure d’Electricite (Supelec).
Equivalent to a Master in Engineering