David R. F. Leach

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Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over-replication of flanking DNA may(More)
It has long been known that the 5' to 3' polarity of DNA synthesis results in both a leading and lagging strand at all replication forks. Until now, however, there has been no evidence that leading or lagging strands are spatially organized in any way within a cell. Here we show that chromosome segregation in Escherichia coli is not random but is driven in(More)
High-throughput studies of the 6,200 genes of Saccharomyces cerevisiae have provided valuable data resources. However, these resources require a return to experimental analysis to test predictions. An in-silico screen, mining existing interaction, expression, localization, and phenotype datasets was developed with the aim of selecting minimally(More)
Survival and genome stability are critical characteristics of healthy cells. DNA palindromes pose a threat to genome stability and have been shown to participate in a reaction leading to the formation of inverted chromosome duplications centered around themselves. There is considerable interest in the mechanism of this rearrangement given its likely(More)
The repair of DNA double-strand breaks must be accurate to avoid genomic rearrangements that can lead to cell death and disease. This can be accomplished by promoting homologous recombination between correctly aligned sister chromosomes. Here, using a unique system for generating a site-specific DNA double-strand break in one copy of two replicating(More)
DNA double-strand breaks can be repaired by homologous recombination involving the formation and resolution of Holliday junctions. In Escherichia coli, the RuvABC resolvasome and the RecG branch-migration enzyme have been proposed to act in alternative pathways for the resolution of Holliday junctions. Here, we have studied the requirements for RuvABC and(More)
DNA palindromes are hotspots for DNA double strand breaks, inverted duplications and intra-chromosomal translocations in a wide spectrum of organisms from bacteria to humans. These reactions are mediated by DNA secondary structures such as hairpins and cruciforms. In order to further investigate the pathways of formation and cleavage of these structures, we(More)
DNA damage checkpoints exist to promote cell survival and the faithful inheritance of genetic information. It is thought that one function of such checkpoints is to ensure that cell division does not occur before DNA damage is repaired. However, in unicellular organisms, rapid cell multiplication confers a powerful selective advantage, leading to a dilemma.(More)
The expansion of CAG·CTG repeat tracts is responsible for several neurodegenerative diseases, including Huntington disease and myotonic dystrophy. Understanding the molecular mechanism of CAG·CTG repeat tract expansion is therefore important if we are to develop medical interventions limiting expansion rates. Escherichia coli provides a simple and tractable(More)
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