Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM.

ABSTRACT: In preparation for bidirectional DNA replication, the origin recognition complex (ORC) loads two hexameric MCM helicases to form a head-to-head double hexamer around DNA^1,2. The mechanism of MCM double-hexamer formation is debated. Single-molecule experiments have suggested a sequential mechanism, in which the ORC-dependent loading of the first hexamer drives the recruitment of the second hexamer³. By contrast, biochemical data have shown that two rings are loaded independently via the same ORC-mediated mechanism, at two inverted DNA sites^4,5. Here we visualize MCM loading using time-resolved electron microscopy, and identify intermediates in the formation of the double hexamer. We confirm that both hexamers are recruited via the same interaction that occur

SUBMITTER: Miller TCR 

PROVIDER: S-EPMC6887548 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature