RRC ID 30705
著者 Shimada A, Kawasoe Y, Hata Y, Takahashi TS, Masui R, Kuramitsu S, Fukui K.
タイトル MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner.
ジャーナル 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.
巻・号 280(14)
ページ 3467-79
公開日 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
引用数 13
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 Thermus thermophilus expression plasmid set TEx18D08 (THR007280) TEx18C04 (THR007252).