The archaeal RecJ-like proteins: nucleases and ex-nucleases with diverse roles in replication and repair

Abstract

RecJ proteins belong to the DHH superfamily of phosphoesterases that has members in all three domains of life. In bacteria, the archetypal RecJ is a 5′ → 3′ ssDNA exonuclease that functions in homologous recombination, base excision repair and mismatch repair, while in eukaryotes, the RecJ-like protein Cdc45 (which has lost its nuclease activity) is a key component of the CMG (Cdc45–MCM–GINS) complex, the replicative DNA helicase that unwinds double-stranded DNA at the replication fork. In archaea, database searching identifies genes encoding one or more RecJ family proteins in almost all sequenced genomes. Biochemical analysis has confirmed that some but not all of these proteins are components of archaeal CMG complexes and has revealed a surprising diversity in mode of action and substrate preference. In addition to this, some archaea encode catalytically inactive RecJ-like proteins, and others a mix of active and inactive proteins, with the inactive proteins being confined to structural roles only. Here, I summarise current knowledge of the structure and function of the archaeal RecJ-like proteins, focusing on similarities and differences between proteins from different archaeal species, between proteins within species and between the archaeal proteins and their bacterial and eukaryotic relatives. Models for RecJ-like function are described and key areas for further study highlighted.

Haloferax volcanii —a model archaeon for studying DNA replication and repair

“…The DHH superfamily has undergone an expansion event within the archaea (specifically within the phylum Euryarchaea), where multiple species now encode several RecJ-like proteins. To date, every archaeal species studied encodes at least one RecJ protein [ 107 ] and while some homologues retain previous identities, others evolved quickly and developed novel roles [ 96 ]. RecJ proteins in archaea have now been implicated in DNA repair and replication, some have lost all activity, while the roles of many remain unknown [ 96 ].…”

“…The identity of the Cdc45 homologue in H. volcanii is also an open question. Preliminary work has identified four RecJ homologues: RecJ1 (HVO_0073), RecJ2 (HVO_1147), RecJ3 (HVO_1018) and RecJ4 (HVO_2889) [ 107 ]. Based on similarity to Cdc45, GAN and RecJ proteins in general, it has been proposed that one (or more) of these RecJ homologues function as the Cdc45 homologue in H. volcanii [ 71 ].…”