In eukaryotes, the CMG (Cdc45, MCM, GINS) complex functions as the replicative helicase and plays a key role in DNA replication. Archaeal homologs of the eukaryotic MCM and GINS proteins have been identified but until recently no homolog of the CDC45 protein was known. The lack of a CDC45 homologue was puzzling and was attributed to the lower complexity of the archaeal replication machinery compared to that of eukaryotes. This hypothesis was refuted by the recent discovery of archaeal GINS-associated nuclease (GAN) that was identified via its interaction with the GINS complex and belongs to the RecJ family of the DHH hydrolase superfamily. Here we present results of computational analysis that confirm and extend the recent hypothesis that CDC45 is the eukaryotic ortholog of RecJ. In depth comparative genomic analysis led to the identification of at least one RecJ homolog in all sequenced archaeal genomes, with a single exception. Combined with phylogenetic tree reconstruction of diverse archaeal DHH subfamilies, this analysis yields a complex scenario of RecJ family evolution in Archaea which includes independent inactivation of the nuclease domain in Crenarchaeota and Halobacteria, and loss of this domain in Methanococcales. We hypothesize that inactivated RecJ homologs are dedicated structural components of replication complexes. A complex of a RecJ homolog, MCM and GINS (RMG) is homologous and functionally analogous to the eukaryotic CMG complex.
Citation: Biology Direct
Pub Type: Journals
eukaryotes, Archaeal, MCM, GINS, Cdc45