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Nat Struct Mol Biol. 2016 Oct;23(10):891-898. doi: 10.1038/nsmb.3286. Epub 2016 Aug 29.

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative.

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Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA.
MRSA Research Center, The University of Chicago, Chicago, Illinois, USA.


Methicillin-resistant Staphylococcus aureus (MRSA) is a public-health threat worldwide. Although the mobile genomic island responsible for this phenotype, staphylococcal cassette chromosome (SCC), has been thought to be nonreplicative, we predicted DNA-replication-related functions for some of the conserved proteins encoded by SCC. We show that one of these, Cch, is homologous to the self-loading initiator helicases of an unrelated family of genomic islands, that it is an active 3'-to-5' helicase and that the adjacent ORF encodes a single-stranded DNA-binding protein. Our 2.9-Å crystal structure of intact Cch shows that it forms a hexameric ring. Cch, like the archaeal and eukaryotic MCM-family replicative helicases, belongs to the pre-sensor II insert clade of AAA+ ATPases. Additionally, we found that SCC elements are part of a broader family of mobile elements, all of which encode a replication initiator upstream of their recombinases. Replication after excision would enhance the efficiency of horizontal gene transfer.

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