Department of Microbial Biotechnology, Centro Nacional de Biotecnología, CNB-CSIC, 28049 Madrid, Spain.
Cells. 2021 May 31;10(6):1357. doi: 10.3390/cells10061357.
The DNA damage checkpoint protein DisA and the branch migration translocase RecG are implicated in the preservation of genome integrity in reviving haploid spores. DisA synthesizes the essential cyclic 3', 5'-diadenosine monophosphate (c‑di-AMP) second messenger and such synthesis is suppressed upon replication perturbation. , c-di-AMP synthesis is suppressed when DisA binds DNA structures that mimic stalled or reversed forks (gapped forks or Holliday junctions [HJ]). RecG, which does not form a stable complex with DisA, unwinds branched intermediates, and in the presence of a limiting ATP concentration and HJ DNA, it blocks DisA-mediated c-di-AMP synthesis. DisA pre-bound to a stalled or reversed fork limits RecG-mediated ATP hydrolysis and DNA unwinding, but not if RecG is pre-bound to stalled or reversed forks. We propose that RecG-mediated fork remodeling is a genuine activity, and that DisA, as a molecular switch, limits RecG-mediated fork reversal and fork restoration. DisA and RecG might provide more time to process perturbed forks, avoiding genome breakage.
DNA 损伤检查点蛋白 DisA 和分支迁移转位酶 RecG 参与了在复活单倍体孢子时维持基因组完整性。DisA 合成必需的环 3'，5'-二腺苷酸单磷酸（c-di-AMP）第二信使，这种合成在复制扰动时受到抑制。当 DisA 结合模拟停滞或反转叉（缺口叉或 Holliday 结 [HJ]）的 DNA 结构时，c-di-AMP 合成受到抑制。RecG 不与 DisA 形成稳定复合物，可解开分支中间体，并且在有限的 ATP 浓度和 HJ DNA 存在下，它可阻断 DisA 介导的 c-di-AMP 合成。预先结合到停滞或反转叉上的 DisA 限制了 RecG 介导的 ATP 水解和 DNA 解旋，但如果 RecG 预先结合到停滞或反转叉上则不会受到限制。我们提出 RecG 介导的叉重排是一种真正的活性，而 DisA 作为分子开关，限制了 RecG 介导的叉反转和叉修复。DisA 和 RecG 可能会为处理受扰的叉提供更多的时间，从而避免基因组断裂。
