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bioRxiv · 10.1101/2020.11.23.394155

DisA limits RecA- and RadA/Sms-mediated replication fork remodelling to prevent genome instability

Torres, R.·Alonso, J. C.
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Abstract

The DisA diadenylate cyclase (DAC), the DNA helicase RadA/Sms and the RecA recombinase are required to prevent a DNA replication stress during the revival of haploid Bacillus subtilis spores. Moreover, disA, radA and recA are epistatic among them in response to DNA damage. We show that DisA inhibits the ATPase activity of RadA/Sms C13A by competing for single-stranded (ss) DNA. In addition, DisA inhibits the helicase activity of RadA/Sms. RecA filamented onto ssDNA interacts with and recruits DisA and RadA/Sms onto branched DNA intermediates. In fact, RecA binds a reversed fork and facilitates RadA/Sms-mediated unwinding to restore a 3'-fork intermediate, but DisA inhibits it. Finally, RadA/Sms inhibits DisA DAC activity, but RecA counters this negative effect. We propose that RecA, DisA and RadA/Sms interactions, which are mutually exclusive, limit remodelling of stalled replication forks. DisA, in concert with RecA and/or RadA/Sms, indirectly contributes to template switching or lesion bypass, prevents fork breakage and facilitates the recovery of c-di-AMP levels to re-initiate cell proliferation. Subject CategoriesGenomic stability & Dynamics

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Torres, R., Alonso, J. C.. 2020-11-23. DisA limits RecA- and RadA/Sms-mediated replication fork remodelling to prevent genome instability. https://doi.org/10.1101/2020.11.23.394155

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