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

ABSTRACT: DNA replication initiation requires 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). Three distinct mechanisms have been proposed to facilitate human MCM loading, but the physiological relevance of each pathway remains unclear. Here, we investigate the evolutionary conservation of these pathways using an AlphaFold-guided structural phylogenetics approach. Our analyses reveal that ORC6, an ORC subunit thought to be essential for origin licensing in vivo, has been lost in multiple metazoan lineages. Despite this loss, many of these species retain an element in ORC3, the ORC3 tether, that can interact with M

SUBMITTER: Olivia Hunker 

PROVIDER: S-SCDT-10_1038-S44318-025-00628-5 | biostudies-other |

REPOSITORIES: biostudies-other