Kinetic Model of DNA Replication in Eukaryotic Organisms

Abstract

(J.B.) and abensim@pasteur.fr (A.B.) We formulate a kinetic model of DNA replication that quantitatively describes recent results on DNA replication in the in vitro system of Xenopus laevis prior to the mid-blastula transition. The model describes well a large amount of different data within a simple theoretical framework. This allows one, for the first time, to determine the parameters governing the DNA replication program in a eukaryote on a genome-wide basis. In particular, we have determined the frequency of origin activation in time and space during the cell cycle. Although we focus on a specific stage of development, this model can easily be adapted to describe replication in many other organisms, including budding yeast.

DNA replication timing: random thoughts about origin firing

“…To avoid the random gap problem, it has been argued that there must be some mechanism to coordinate origin firing so as to avoid large random gaps 22 . Surprisingly, in two cases in which the distribution of origin firing has been carefully examined -frog embryo extracts and fission yeast -the distribution was in fact random and large random gaps were observed 8,9,23,24 .…”

Nucleation and growth in one dimension. I. The generalized Kolmogorov-Johnson-Mehl-Avrami model

“…Although most of the applications of the KJMA model have been to the study of phase transformations in threedimensional systems, similar ideas have been applied to a wide range of one-dimensional problems, such as Rényi's car-parking problem [12] and the coarsening of long parallel droplets [13]. Recently, we have shown that the onedimensional KJMA model can also be used to describe DNA replication in higher organisms [19]. Briefly, in higher organisms (eukaryotes), DNA replication is initiated at multiple origins throughout the genome.…”

“…Recently, Herrick et al used a more efficient algorithm [19]. Specifically, they recorded the positions of moving island edges only.…”

“…5). The first of these, the "double-list" algorithm, extends the method of Herrick et al [19]. The second of these, the "phantom-nuclei" algorithm, is inspired by the original work of Avrami [3].…”

Study of the interaction of DNA and histones by spin-stretching and droplet evaporation

“…Such methods include dynamic molecular combing (meniscus moving on a coverslip [14]), spin-stretching [8,9], the evaporation of small droplets of DNA solutions [15,16], the stretching of DNA with a cover slip [17], the mechanical movement of a *Corresponding author (email: 51888lyy@sina.com) meniscus [18], droplet motion driven by a nitrogen gas flow [19], the precise control of the meniscus motion [20], the ordered stretching of DNA between micro fabricated polystyrene lines [21], the moving droplet method [22] and aligning DNA molecules on a SiO 2 surface using a diamond-like carbon (DLC) thin film [23]. Combined with other techniques, the applications of the molecular combing method can be widened to include positioning genes on chromosomes [14], the genomic studies of DNA replication [24], the observation of transcription on a single combed DNA [25], the study of the interaction between DNA and enzymes [26,27] and the self-organized DNA network between two cover slips [28].Eukaryotic genes do not exist as naked DNA molecules in the nucleus of a cell. Instead, they combine with particular proteins, especially the basic proteins called histones, to form a substance known as chromatin [29].…”