AlphaFold-guided phylogenetic analyses suggest surprising heterogeneity in metazoan replication origin licensing mechanisms.

ABSTRACT: DNA replication initiation is a tightly regulated process that requires the coordinated assembly of replication machineries throughout the genome. During the first step of initiation, origin licensing, the MCM replicative helicase motor is loaded onto replication origins by the origin recognition complex (ORC) as a head-to-head double hexamer complex. Distinct mechanisms have been proposed to facilitate human MCM double hexamer loading, but the physiological relevance of each of them remains unclear. Here, we investigate the evolutionary conservation of these pathways using an AlphaFold-guided structural phylogenetics approach. Our analyses reveal that ORC6, a subunit of ORC previously thought to be essential for origin licensing in vivo, has been lost in multiple metazoan lineages. Despit

SUBMITTER: Hunker O 

PROVIDER: S-EPMC12759066 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature