Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates
| Autor: | Karl-Peter Hopfner, Sophia Hartung, Katharina Büttner, Gregor Witte |
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| Rok vydání: | 2007 |
| Předmět: |
Molecular Sequence Data
Cell Cycle Proteins Biology Crystallography X-Ray Cyclase chemistry.chemical_compound Protein structure Bacterial Proteins Holliday junction DNA Breaks Double-Stranded Thermotoga maritima Histone octamer Amino Acid Sequence Molecular Biology Recombination Genetic Spores Bacterial DNA Cruciform Binding Sites Cell Biology G2-M DNA damage checkpoint Protein Structure Tertiary Solutions Biochemistry chemistry Phosphorus-Oxygen Lyases Holliday junction recognition protein Cyclase activity DNA Dinucleoside Phosphates Bacillus subtilis |
| Zdroj: | Molecular cell. 30(2) |
| ISSN: | 1097-4164 |
| Popis: | To reveal mechanisms of DNA damage checkpoint initiation, we structurally and biochemically analyzed DisA, a protein that controls a Bacillus subtilis sporulation checkpoint in response to DNA double-strand breaks. We find that DisA forms a large octamer that consists of an array of an uncharacterized type of nucleotide-binding domain along with two DNA-binding regions related to the Holliday junction recognition protein RuvA. Remarkably, the nucleotide-binding domains possess diadenylate cyclase activity. The resulting cyclic diadenosine phosphate, c-di-AMP, is reminiscent but distinct from c-di-GMP, an emerging prokaryotic regulator of complex cellular processes. Diadenylate cyclase activity is unaffected by linear DNA or DNA ends but strongly suppressed by branched nucleic acids such as Holliday junctions. Our data indicate that DisA signals DNA structures that interfere with chromosome segregation via c-di-AMP. Identification of the diadenylate cyclase domain in other eubacterial and archaeal proteins implies a more general role for c-di-AMP in prokaryotes. |
| Databáze: | OpenAIRE |
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