DNA integrity scanning protein, diadenylate cyclase, delays [SW|sporulation] in the case of chromosome damage, the DisA-dependent checkpoint arrests [SW|DNA replication] during B. subtilis spore outgrowth until the germinating spores genome is free of damage
function
control of [SW|sporulation] initiation
product
DNA integrity scanning protein, has diadenylate cyclase activity
Genomic Context
categories
[category|SW 1|Cellular processes] → [category|SW 1.1|Cell envelope and cell division] → [category|SW 1.1.8|Cell division] → [category|SW 1.1.8.2|Other genes][category|SW 2|Metabolism] → [category|SW 2.5|Nucleotide metabolism] → [category|SW 2.5.3|Metabolism of signalling nucleotides][category|SW 4|Lifestyles] → [category|SW 4.2|Sporulation] → [category|SW 4.2.3|Sporulation/ other][category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.1|General stress proteins (controlled by SigB)][category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.2|Cell envelope stress proteins (controlled by SigM, V, W, X, Y)][category|SW 4|Lifestyles] → [category|SW 4.3|Coping with stress] → [category|SW 4.3.4|Heat shock proteins]Gene
Coordinates
107,476 108,558
Phenotypes of a mutant
a [gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA] [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] double mutant or [gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA] [gene|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|cdaS] [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] triple mutant is not viable on complex medium; however, the mutant grows at low potassium concentration (0.1 mM) [pubmed|28420751]reduced spore survival after infrared exposure [pubmed|28961460]altered morphology on MSgg medium [pubmed|29588402]plant root colonization defect [pubmed|29588402]The protein
Catalyzed reaction/ biological activity
synthesis of c-di-AMP from two molecules of ATP [Pubmed|23192352,21566650]binds [protein|A44D4677FB70BE8F554BF1001A500F817C7DA95F|RecA] to inhibit its activity [pubmed|30916351]Protein family
DisA family (single member, according to UniProt)[SW|Domains]
contains a [SW|DAC domain] for the synthesis of c-di-AMP [Pubmed|18439896][SW|Cofactors]
Mn2+ [pubmed|26014055]Effectors of protein activity
[protein|151F226370D225776F3FE7EA4901485095F1AC45|RadA] is an inhibitor of [protein|2B091CCEE9E34D659771E39B1FC9050A145048AB|DisA] activity [Pubmed|23760274]the presence of potassium results in enhanced activity [pubmed|28420751]Structure
[PDB|3C23] [Pubmed|18439896][SW|Localization]
see a [http://download.cell.com/mmcs/journals/0092-8674/PIIS0092867406005034.mmc12.avi video] showing the movement of DisA in the cell (in real time) [Pubmed|16713562]forms discrete globular foci in germinating spres that colocalize with the nucleoid [Pubmed|24244006]forms rapidly moving focus that pausesat [protein|A44D4677FB70BE8F554BF1001A500F817C7DA95F|RecA]-mediated recombination intermediates upon induction of DNA damage during spore development [pubmed|30916351]additional information
subject to Clp-dependent proteolysis upon glucose starvation [pubmed|17981983]Expression and Regulation
Operons
genes
[gene|908DB17A39D518E84977250C55825E77FA02E391|ctsR]-[gene|CA0939064E70A97434FA450A69E779FD89880613|mcsA]-[gene|7B1B664A1AE1F641E8E7D9E2894D5C8FFFA92948|mcsB]-[gene|86A2F2F65290F4471D6FD03B694821C66C180D8A|clpC]-[gene|151F226370D225776F3FE7EA4901485095F1AC45|radA]-[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]
description
[Pubmed|8793870]
sigma factors
[protein|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM]: sigma factor, [Pubmed|17434969], in [regulon|081DF3EE9FA56209D648C7677188C61CE3AA8E41|SigM regulon][protein|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA]: sigma factor, [Pubmed|8793870], in [regulon|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA regulon][protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB]: sigma factor, [pubmed|8793870] [pubmed|11544224], in [regulon|580011DE5DC40EC9E7E0512791D328FAA010DCB8|SigB regulon][protein|CFF318EE6CACDEE763FBF96A2ABB46E944679AAA|SigF]: sigma factor, [Pubmed|16497325], in [regulon|CFF318EE6CACDEE763FBF96A2ABB46E944679AAA|SigF regulon]regulatory mechanism
[protein|908DB17A39D518E84977250C55825E77FA02E391|CtsR]: repression, [pubmed|9987115,11179229,16163393,17380125], in [regulon|908DB17A39D518E84977250C55825E77FA02E391|CtsR regulon][protein|2C6386E9A63F410558D168798D077DF91590F454|Spx]: activation, [pubmed|30962353], in [regulon|2C6386E9A63F410558D168798D077DF91590F454|Spx regulon]regulation
expressed during germination and spore outgrowth [Pubmed|24244006]induction during diamide stress ([protein|2C6386E9A63F410558D168798D077DF91590F454|Spx]) [pubmed|30962353]view in new tabgenes
[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]
description
[Pubmed|17434969]
regulation
expressed during germination and spore outgrowth [Pubmed|24244006]view in new tabBiological materials
Mutant
MGNA-B932 ([gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::erm), available at the [https://shigen.nig.ac.jp/bsub/resource/strainGeneDisrupted/detail/1931 NBRP B. subtilis, Japan]GP2142 (''Δ''''[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]''::''tet''), available in [SW|Jörg Stülke]'s labBKG2 (''[gene|151F226370D225776F3FE7EA4901485095F1AC45|radA]-[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::spc''), available in [SW|Jörg Stülke]'s lab1A939 ( ''disA''::''tet''), [Pubmed|16713562], available at [http://pasture.asc.ohio-state.edu/BGSC/getdetail.cfm?bgscid=1A939&Search=1A939 BGSC]GP2222 ([gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::cat [gene|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|cdaS]::ermC [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::''tet''), available in [SW|Jörg Stülke]'s lab, the mutant is only viable on minimal medium at low potassium concentration [pubmed|28420751]BKE00880 ([gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::erm trpC2) available at [http://www.bgsc.org/getdetail.php?bgscid=BKE00880 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CCCTTTTTTCTCTTTTTCCA, downstream forward: _UP4_TGATTTCGGTTAAAACCTTABKK00880 ([gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::kan trpC2) available at [http://www.bgsc.org/getdetail.php?bgscid=BKK00880 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CCCTTTTTTCTCTTTTTCCA, downstream forward: _UP4_TGATTTCGGTTAAAACCTTAGP2715 (''Δ''''[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]''::''spc''), available in [SW|Jörg Stülke]'s labGP2752 (''Δ''''[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]''::''cat''), available in [SW|Jörg Stülke]'s labGP2782 (''Δ''''[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]''::''kan''), available in [SW|Jörg Stülke]'s labExpression vectors
IPTG inducible expression of His-''disA'' in ''E. coli'': pGP2563 (in [http://biochem.web.utah.edu/hill/links/pET19b.pdf pET19b]), available in [SW|Jörg Stülke]'s labtwo-hybrid system
B. pertussis adenylate cyclase-based bacterial two hybrid system ([SW|BACTH]), available in [SW|Fabian Commichau]'s labReferences
Reviews
22933559,18714086,25869574,23812326,30224435 Original publications
24244006,8793870,9987115,16713562,23760274,11544224,17434969,18439896,16713555,12493822,21566650,23192352,23608499,25616256,26014055,27150552,28420751,28511132,28961460,29536659,29588402,30877841,30916351