Biology – Quantitative Biology – Quantitative Methods
Scientific paper
2003-11-24
Biology
Quantitative Biology
Quantitative Methods
To appear at Cell Cycle (vol 3, no 2, 2004) 14 pages, 4 figures. How physics can help solve a long-standing mysteries in DNA r
Scientific paper
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.
Bechhoefer John
Bensimon Aaron
Herrick John
Jun Suckjoon
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