disA
168
DNA integrity scanning protein, diadenylate cyclase, delays [wiki|sporulation] in the case of chromosome damage, the DisA-dependent checkpoint arrests [wiki|DNA replication] during B. subtilis spore outgrowth until the germinating spores genome is free of damage
locus
BSU_00880
Molecular weight
40.58 kDa
pI
5.57
function
control of [wiki|sporulation] initiation, synthesis of [metabolite|c-di-AMP]
product
DNA integrity scanning protein, has diadenylate cyclase activity
essential
no
ec
2.7.7.85
synonyms
disA, yacK
Outlinks
Genomic Context
Categories containing this gene/protein
List of homologs in different organisms, belongs to COG1623 (Galperin et al., 2021)
This gene is a member of the following regulons
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 [metabolite|c-di-AMP] from two molecules of [metabolite|ATP] [Pubmed|23192352,21566650]
2 [metabolite|ATP] --> [metabolite|c-di-AMP] + 2 [metabolite|diphosphate] [Pubmed|23192352,21566650]
binds to abasic DNA lesions [pubmed|37250769]
binds [protein|A44D4677FB70BE8F554BF1001A500F817C7DA95F|recA] to inhibit its activity [pubmed|30916351]
limits [protein|24B1C2A663A5B7C45940272595868F9F05A04A7B|recG] activities at stalled or reversed replication forks [pubmed|34073022]
limits [protein|7EBC90946E7167A3B0212193873855CAE0EFF7D4|ruvA]-[protein|8DFD57B73FE5D49BB547E050182A96CE6E8BFF77|ruvB]-mediated fork remodeling and [protein|ED1E2011C7E43A8B7E9FD9A471BC11B9DEA73177|recU]-mediated HJ cleavage to provide time for damage removal and replication restart in order to preserve genome integrity [pubmed|34768753]
Protein family
DisA family (single member, according to UniProt)
[wiki|Domains]
contains a [wiki|DAC domain] for the synthesis of [metabolite|c-di-AMP] [Pubmed|18439896]
[wiki|DAC domain] (aa 11-149) (according to UniProt)
[wiki|Cofactors]
Mn2+ [pubmed|26014055]
Structure
[PDB|3C23] [Pubmed|18439896]
[AF|P37573]
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]
[wiki|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 pauses at [protein|A44D4677FB70BE8F554BF1001A500F817C7DA95F|recA]-mediated recombination intermediates upon induction of DNA damage during spore development [pubmed|30916351]
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]
regulation
expressed during germination and spore outgrowth [Pubmed|24244006]
regulatory mechanism
[protein|908DB17A39D518E84977250C55825E77FA02E391|ctsR]: repression, [pubmed|9987115,11179229,16163393,17380125], in [regulon|protein:908DB17A39D518E84977250C55825E77FA02E391|ctsR regulon]
[protein|2C6386E9A63F410558D168798D077DF91590F454|spx]: activation, [pubmed|30962353], in [regulon|protein:2C6386E9A63F410558D168798D077DF91590F454|spx regulon]
sigma factors
[protein|081DF3EE9FA56209D648C7677188C61CE3AA8E41|sigM]: sigma factor, [Pubmed|17434969], in [regulon|protein:081DF3EE9FA56209D648C7677188C61CE3AA8E41|sigM regulon]
[protein|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|sigA]: sigma factor, [Pubmed|8793870], in [regulon|protein:360F48D576DE950DF79C1A2677B7A35A8D8CC30C|sigA regulon]
[protein|580011DE5DC40EC9E7E0512791D328FAA010DCB8|sigB]: sigma factor, [pubmed|8793870] [pubmed|11544224], in [regulon|protein:580011DE5DC40EC9E7E0512791D328FAA010DCB8|sigB regulon]
[protein|CFF318EE6CACDEE763FBF96A2ABB46E944679AAA|sigF]: sigma factor, [Pubmed|16497325], in [regulon|protein:CFF318EE6CACDEE763FBF96A2ABB46E944679AAA|sigF regulon]
genes
[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]
description
[Pubmed|17434969]
regulation
expressed during germination and spore outgrowth [Pubmed|24244006]
Biological 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 [wiki|Jörg Stülke]'s lab
BKG2 ([gene|151F226370D225776F3FE7EA4901485095F1AC45|radA]-[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::''spc''), available in [wiki|Jörg Stülke]'s lab
1A939 ([gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|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 [wiki|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://bgsc.org/getdetail.php?bgscid=BKE00880 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CCCTTTTTTCTCTTTTTCCA, downstream forward: _UP4_TGATTTCGGTTAAAACCTTA
BKK00880 ([gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::kan trpC2) available at [http://bgsc.org/getdetail.php?bgscid=BKK00880 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CCCTTTTTTCTCTTTTTCCA, downstream forward: _UP4_TGATTTCGGTTAAAACCTTA
GP2715 (Δ[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::''spc''), available in [wiki|Jörg Stülke]'s lab
GP2752 (Δ[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::''cat''), available in [wiki|Jörg Stülke]'s lab
GP2782 (Δ[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]::''kan''), available in [wiki|Jörg Stülke]'s lab
Expression vectors
IPTG inducible expression of His-[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] in ''E. coli'': pGP2563 (in [http://biochem.web.utah.edu/hill/links/pET19b.pdf pET19b]), available in [wiki|Jörg Stülke]'s lab [pubmed|23192352]
two-hybrid system
B. pertussis adenylate cyclase-based bacterial two hybrid system ([wiki|BACTH]), available in [wiki|Fabian Commichau]'s lab
References
Reviews
Original Publications
Page visits: 11124
Time of last update: 2024-12-18 11:31:39
Author of last update: Jstuelk