In response to DNA damage, cells activate checkpoint signaling cascades to control cell-cycle progression and elicit DNA repair in order to maintain genomic integrity. The sensing and repair of lesions is critical for Bacillus subtilis cells entering the developmental process of sporulation as damaged DNA may prevent the cells from completing spore morphogenesis. We report the identification of the protein DisA (DNA integrity scanning protein, annotated YacK), which is required to delay the initiation of sporulation in response to chromosomal damage. DisA is a nonspecific DNA binding protein that forms a single focus, which moves rapidly within the bacterial cell, pausing at sites of DNA damage. We propose that the DisA focus scans along the chromosomes searching for lesions. Upon encountering a lesion, DisA delays entry into sporulation until the damage is repaired.
Bibliographical noteFunding Information:
We thank R. Losick (Harvard University, USA), in whose laboratory the preliminary experiments for this study were performed; and J. Errington (Oxford University, UK), A. Grossman and M. Berkmen (MIT, USA), and M. Kupiec (Tel-Aviv University, IL) for strains and reagents. We thank R. Losick (Harvard University, USA), D. Rudner (Harvard Medical School, USA), D. Kearns (Indiana University, USA), A. Taraboulos (Hebrew University, IL), and members of the Ben-Yehuda laboratory for valuable comments on the manuscript. This work was supported by the Human Frontier Science Program (HFSP) Career Development Award (CDA0046/2004), by the Israel Science Foundation (ISF grant 1401/04), and by the Bruno-Goldberg Endowment to S.B.-Y.