Topologies of complexes containing O6-alkylguanine-DNA alkyltransferase and DNA.

ABSTRACT: The mutagenic and cytotoxic effects of many alkylating agents are reduced by O(6)-alkylguanine-DNA alkyltransferase (AGT). In humans, this protein not only protects the integrity of the genome, but also contributes to the resistance of tumors to DNA-alkylating chemotherapeutic agents. Here we describe and test models for cooperative multiprotein complexes of AGT with single-stranded and duplex DNAs that are based on in vitro binding data and the crystal structure of a 1:1 AGT-DNA complex. These models predict that cooperative assemblies contain a three-start helical array of proteins with dominant protein-protein interactions between the amino-terminal face of protein n and the carboxy-terminal face of protein n+3, and they predict that binding duplex DNA does not require large changes in

SUBMITTER: Adams CA 

PROVIDER: S-EPMC2736636 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature