Organization of DNA Replication Origin Firing in Xenopus Egg Extracts: The Role of Intra-S Checkpoint

Genes

Olivier Hyrien¹  Olivier Haccard²  Hemalatha Narassimprakash²  Kathrin Marheineke²  Diletta Ciardo²  Arach Goldar²  Jean-Michel Arbona³  Benjamin Audit⁴ 

[1] Institut de Biologie de l’Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France;Institute of Integrative Biology of the Cell (I2BC), CNRS, CEA, University Paris Sud, 1, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France;University Lyon, ENS de Lyon, Laboratoire de Biologie et Modélisation de la Cellule, University Claude Bernard Lyon 1, CNRS UMR5239, INSERM U1210, 46 Allé d’Italie Site Jacques Monod, 69007 Lyon, France;University Lyon, ENS de Lyon, University Claude Bernard Lyon 1, CNRS, Laboratoire de Physique, 69342 Lyon, France;

关键词: DNA replication;    checkpoint;    mathematical modelling;    minimal model;    origin firing;   

DOI  :  10.3390/genes12081224

来源: DOAJ

【 摘 要 】

During cell division, the duplication of the genome starts at multiple positions called replication origins. Origin firing requires the interaction of rate-limiting factors with potential origins during the S(ynthesis)-phase of the cell cycle. Origins fire as synchronous clusters which is proposed to be regulated by the intra-S checkpoint. By modelling the unchallenged, the checkpoint-inhibited and the checkpoint protein Chk1 over-expressed replication pattern of single DNA molecules from Xenopus sperm chromatin replicated in egg extracts, we demonstrate that the quantitative modelling of data requires: (1) a segmentation of the genome into regions of low and high probability of origin firing; (2) that regions with high probability of origin firing escape intra-S checkpoint regulation and (3) the variability of the rate of DNA synthesis close to replication forks is a necessary ingredient that should be taken in to account in order to describe the dynamic of replication origin firing. This model implies that the observed origin clustering emerges from the apparent synchrony of origin firing in regions with high probability of origin firing and challenge the assumption that the intra-S checkpoint is the main regulator of origin clustering.

【 授权许可】

Unknown