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Chi hotspots trigger a conformational change in the helicase-like domain of AddAB to activate homologous recombination

  • Neville S. Gilhooly
  • , Carolina Carrasco
  • , Benjamin Gollnick
  • , Martin Wilkinson
  • , Dale B. Wigley
  • , Fernando Moreno-Herrero
  • , Mark S. Dillingham*
  • *Corresponding author for this work

    Research output: Contribution to journal › Article (Academic Journal) › peer-review

    7 Citations (Scopus)
    377 Downloads (Pure)

    Abstract

    In bacteria, the repair of double-stranded DNA breaks is modulated by Chi sequences. These are recognised by helicase-nuclease complexes that process DNA ends for homologous recombination. Chi activates recombination by changing the biochemical properties of the helicase-nuclease, transforming it from a destructive exonuclease into a recombination-promoting repair enzyme. This transition is thought to be controlled by the Chi-dependent opening of a molecular latch, which enables part of the DNA substrate to evade degradation beyond Chi. Here, we show that disruption of the latch improves Chi recognition efficiency and stabilizes the interaction of AddAB with Chi, even in mutants that are impaired for Chi binding. Chi recognition elicits a structural change in AddAB that maps to a region of AddB which resembles a helicase domain, and which harbours both the Chi recognition locus and the latch. Mutation of the latch potentiates the change and moderately reduces the duration of a translocation pause at Chi. However, this mutant displays properties of Chi-modified AddAB even in the complete absence of bona fide hotspot sequences. The results are used to develop a model for AddAB regulation in which allosteric communication between Chi binding and latch opening ensures quality control during recombination hotspot recognition.

    Original languageEnglish
    Article numbergkv1543
    Pages (from-to)2727-2741
    Number of pages15
    JournalNucleic Acids Research
    Volume44
    Issue number6
    Early online date13 Jan 2016
    DOIs
    Publication statusPublished - 7 Apr 2016

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