| RRC ID |
30705
|
| Author |
Shimada A, Kawasoe Y, Hata Y, Takahashi TS, Masui R, Kuramitsu S, Fukui K.
|
| Title |
MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner.
|
| Journal |
FEBS J
|
| Abstract |
In the initial steps of DNA mismatch repair, MutS recognizes a mismatched base and recruits the latent endonuclease MutL onto the mismatch-containing DNA in concert with other proteins. MutL then cleaves the error-containing strand to introduce an entry point for the downstream excision reaction. Because MutL has no intrinsic ability to recognize a mismatch and discriminate between newly synthesized and template strands, the endonuclease activity of MutL is strictly regulated by ATP-binding in order to avoid nonspecific degradation of the genomic DNA. However, the activation mechanism for its endonuclease activity remains unclear. In this study, we found that the coexistence of a mismatch, ATP and MutS unlocks the ATP-binding-dependent suppression of MutL endonuclease activity. Interestingly, ATPase-deficient mutants of MutS were unable to activate MutL. Furthermore, wild-type MutS activated ATPase-deficient mutants of MutL less efficiently than wild-type MutL. We concluded that ATP hydrolysis by MutS and MutL is involved in the mismatch-dependent activation of MutL endonuclease activity.
|
| Volume |
280(14)
|
| Pages |
3467-79
|
| Published |
2013-7-1
|
| DOI |
10.1111/febs.12344
|
| PMID |
23679952
|
| MeSH |
Adenosine Triphosphatases / antagonists & inhibitors
Adenosine Triphosphatases / chemistry
Adenosine Triphosphatases / metabolism*
Adenosine Triphosphate / chemistry*
DNA Mismatch Repair
Enzyme Activation
Hydrolysis
Kinetics
MutS DNA Mismatch-Binding Protein / chemistry
MutS DNA Mismatch-Binding Protein / metabolism*
Plasmids / genetics
Protein Structure, Tertiary
Thermus thermophilus / enzymology*
|
| IF |
4.392
|
| Times Cited |
13
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
Thermus thermophilus expression plasmid set
TEx18D08 (THR007280)
TEx18C04 (THR007252). |
