RESUMO
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.
Assuntos
Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/química , Proteína MutS de Ligação de DNA com Erro de Pareamento/metabolismo , Thermus thermophilus/enzimologia , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/química , Reparo de Erro de Pareamento de DNA , Ativação Enzimática , Hidrólise , Cinética , Proteína MutS de Ligação de DNA com Erro de Pareamento/química , Plasmídeos/genética , Estrutura Terciária de ProteínaRESUMO
Catecholaminergic polymorphic ventricular tachycardia (VT) is characterized by polymorphic VT during exercise, and the association of atrial fibrillation (AF) has been reported. However, the mechanism of AF in this disease and the relationship between VT and AF has been obscured. We described a 13-year-old girl who referred for catheter ablation of exercise-induced paroxysmal AF. Multifocal atrial tachycardia mimicking AF on the surface electrocardiogram originated from multiple pulmonary veins (PVs). While AT became non-inducible after the isolation of four PVs, polymorphic VT was initiated by isoproterenol infusion. Polymorphic VT was suppressed during rapid atrial pacing.