TY - JOUR
T1 - C-di-AMP reports DNA integrity during sporulation in Bacillus subtilis
AU - Oppenheimer-Shaanan, Yaara
AU - Wexselblatt, Ezequiel
AU - Katzhendler, Jehoshua
AU - Yavin, Eylon
AU - Ben-Yehuda, Sigal
PY - 2011/6
Y1 - 2011/6
N2 - The bacterium Bacillus subtilis produces the DNA integrity scanning protein (DisA), a checkpoint protein that delays sporulation in response to DNA damage. DisA scans the chromosome and pauses at sites of DNA lesions. Structural analysis showed that DisA synthesizes the small molecule cyclic diadenosine monophosphate (c-di-AMP). Here, we demonstrate that the intracellular concentration of c-di-AMP rises markedly at the onset of sporulation in a DisA-dependent manner. Furthermore, exposing sporulating cells to DNA-damaging agents leads to a global decrease in the level of this molecule. This drop was associated with stalled DisA complexes that halt c-di-AMP production and with increased levels of the c-di-AMP-degrading enzyme YybT. Reduced c-di-AMP levels cause a delay in sporulation that can be reversed by external supplementation of the molecule. Thus, c-di-AMP acts as a secondary messenger, coupling DNA integrity with progression of sporulation.
AB - The bacterium Bacillus subtilis produces the DNA integrity scanning protein (DisA), a checkpoint protein that delays sporulation in response to DNA damage. DisA scans the chromosome and pauses at sites of DNA lesions. Structural analysis showed that DisA synthesizes the small molecule cyclic diadenosine monophosphate (c-di-AMP). Here, we demonstrate that the intracellular concentration of c-di-AMP rises markedly at the onset of sporulation in a DisA-dependent manner. Furthermore, exposing sporulating cells to DNA-damaging agents leads to a global decrease in the level of this molecule. This drop was associated with stalled DisA complexes that halt c-di-AMP production and with increased levels of the c-di-AMP-degrading enzyme YybT. Reduced c-di-AMP levels cause a delay in sporulation that can be reversed by external supplementation of the molecule. Thus, c-di-AMP acts as a secondary messenger, coupling DNA integrity with progression of sporulation.
KW - B. subtilis
KW - DNA damage checkpoint
KW - DisA
KW - c-di-AMP
KW - sporulation
UR - http://www.scopus.com/inward/record.url?scp=79958009528&partnerID=8YFLogxK
U2 - 10.1038/embor.2011.77
DO - 10.1038/embor.2011.77
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C2 - 21566650
AN - SCOPUS:79958009528
SN - 1469-221X
VL - 12
SP - 594
EP - 601
JO - EMBO Reports
JF - EMBO Reports
IS - 6
ER -