title: The CMG (CDC45/RecJ, MCM, GINS) complex is a conserved component of the DNA replication system in all archaea and eukaryotes.
abstract: BACKGROUND
  In eukaryotes, the CMG (CDC45, MCM, GINS) complex containing the replicative helicase MCM is a key player 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. Two recent developments, namely the discovery of archaeal GINS-associated nuclease (GAN) that belongs to the RecJ family of the DHH hydrolase superfamily and the demonstration of homology between the DHH domains of CDC45 and RecJ, show that at least some Archaea possess a full complement of homologs of the CMG complex subunits. Here we present the results of in-depth phylogenomic analysis of RecJ homologs in archaea.
  
  
  RESULTS
  We confirm and extend the recent hypothesis that CDC45 is the eukaryotic ortholog of the bacterial and archaeal RecJ family nucleases. At least one RecJ homolog was identified in all sequenced archaeal genomes, with the single exception of Caldivirga maquilingensis. These proteins include previously unnoticed remote RecJ homologs with inactivated DHH domain in Thermoproteales. Combined with phylogenetic tree reconstruction of diverse eukaryotic, archaeal and bacterial 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.
  
  
  CONCLUSIONS
  The archaeal complex of a CDC45/RecJ homolog, MCM and GINS is homologous and most likely functionally analogous to the eukaryotic CMG complex, and appears to be a key component of the DNA replication machinery in all Archaea. It is inferred that the last common archaeo-eukaryotic ancestor encoded a CMG complex that contained an active nuclease of the RecJ family. The inactivated RecJ homologs in several archaeal lineages most likely are dedicated structural components of replication complexes.
authors.affiliation: National Center for Biotechnology Information, NLM, National Institutes of Health, Bethesda, Maryland 20894, USA. makarova@ncbi.nlm.nih.gov
authors.forename: Kira S
authors.initials: KS
authors.lastname: Makarova
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
authors.forename: Zvi
authors.initials: Z
authors.lastname: Kelman
mesh_terms: D000595:Amino Acid Sequence; D001105:Archaea / Q000235:genetics* / Q000378:metabolism; D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D019766:Genes, Archaeal; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D019843:Archaeal Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004265:DNA Helicases