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Genome instability

A U-turn for mutagenesis?

Nature Reviews Genetics volume 14, page 7 (2013)Cite this article

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Replication restart from collapsed replication forks can be mutagenic, such as when the end of the newly synthesized leading strand anneals to a nearby homologous (but non-allelic) sequence to restart replication ectopically. Mizuno et al. studied replication restart in fission yeast by analysing the effect of various engineered sequence features on chromosomal replication. They found that even when replication restart occurs correctly, if the replication fork encounters a palindromic sequence within the first few kilobases after restart, the replication machinery occasionally makes a U-turn, generating rearranged daughter chromosomes with absent or multiple centromeres. Such a mechanism might contribute to chromosomal rearrangements and copy number alterations in cancer.

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ORIGINAL RESEARCH PAPER

  1. Mizuno, K. et al. Recombination-restarted replication makes inverted chromosome fusions at inverted repeats. Nature 25 Nov 2012 (doi:10.1038/nature11676)

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  1. Darren J. Burgess
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Burgess, D. A U-turn for mutagenesis?. Nat Rev Genet 14, 7 (2013). https://doi.org/10.1038/nrg3402

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