Signaling from DNA mispairs to mismatch-repair excision sites despite intervening blockades
AUTOR(ES)
Wang, Huixian
RESUMO
Mismatch-repair (MMR) systems promote genomic stability by correction of DNA replication errors. Thus, MMR proteins—prokaryotic MutS and MutL homodimers or their MutSα and MutLα heterodimer homologs, plus accessory proteins—specifically couple mismatch recognition to nascent-DNA excision. In vivo excision-initiation signals—specific nicks in some prokaryotes, perhaps growing 3′ ends or Okazaki-fragment 5′ ends in eukaryotes—are efficiently mimicked in vitro by nicks or gaps in exogenous DNA substrates. In some models for recognition–excision coupling, MutSα bound to mismatches is induced by ATP hydrolysis, or simply by binding of ATP, to slide along DNA to excision-initiation sites, perhaps in association with MutLα and accessory proteins. In other models, MutSα·MutLα complexes remain fixed at mismatches and contact distant excision sites by DNA looping. To challenge the hypothesis that recognition complexes remain fixed, we placed biotin–streptavidin blockades between mismatches and pre-existing nicks. In human nuclear extracts, mismatch efficiently provoked the initiation of excision despite the intervening barriers, as predicted. However, excision progress and therefore mismatch correction were prevented.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=424355Documentos Relacionados
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