Showing papers by "John Bechhoefer published in 2003"

Diffusion-limited loop formation of semiflexible polymers: Kramers theory and the intertwined time scales of chain relaxation and closing

Abstract: We show that Kramers rate theory gives a straightforward, accurate estimate of the closing time τc of a semiflexible polymer that is valid in cases of physical interest. The calculation also reveals how the time scales of chain relaxation and closing are intertwined, illuminating an apparent conflict between two ways of calculating τc in the flexible limit.

Role Of Polymer Loops In DNA Replication

Abstract: Loop formation in long molecules occurs many places in nature, from solutions of carbon nanotubes to polymers inside a cell. In this article, we review theoretical studies of the static and dynamic properties of polymer loops. For example, long polymers must search many configurations to find a "target" binding site, while short polymers are stiff and resist bending. In between, there is an optimal loop size, which balances the entropy of long loops against the energetic cost of short loops. We show that such simple pictures of loop formation can explain several long-standing observations in DNA replication, quantitatively.

Persistence length of chromatin determines origin spacing in Xenopus early-embryo DNA replication: Quantitative comparisons between theory and experiment

Abstract: In Xenopus early embryos, replication origins neither require specific DNA sequences nor is there an efficient S/M checkpoint, even though the whole genome (3 billion bases) is completely duplicated within 10-20 minutes. This leads to the"random-completion problem" of DNA replication in embryos, where one needs to find a mechanism that ensures complete, faithful, timely reproduction of the genome without any sequence dependence of replication origins. We analyze recent DNA replication data in Xenopus laevis egg extracts and find discrepancies with models where replication origins are distributed independently of chromatin structure. Motivated by these discrepancies, we have investigated the role that chromatin looping may play in DNA replication. We find that the loop-size distribution predicted from a wormlike-chain model of chromatin can account for the spatial distribution of replication origins in this system quantitatively. Together with earlier findings of increasing frequency of origin firings, our results can explain the random-completion problem. The agreement between experimental data (molecular combing) and theoretical predictions suggests that the intrinsic stiffness of chromatin loops plays a fundamental biological role in DNA replication in early-embryo Xenopus in regulating the origin spacing.