New Insights Into DNA Repair Revealed by NucS Endonucleases From Hyperthermophilic Archaea

Abstract

Hyperthermophilic Archaea (HA) thrive in high temperature environments and their genome is facing severe stability challenge due to the increased DNA damage levels caused by high temperature. Surprisingly, HA display spontaneous mutation frequencies similar to mesophilic microorganisms, thereby indicating that the former must possess more efficient DNA repair systems than the latter to counteract the potentially enhanced mutation rates under the harsher environment. Although a few repair proteins or enzymes from HA have been biochemically and structurally characterized, the molecular mechanisms of DNA repair of HA remain largely unknown. Genomic analyses of HA revealed that they lack MutS/MutL homologues of the mismatch repair (MMR) pathway and the recognition proteins of the nucleotide excision repair (NER) pathway. Endonucleases play an essential role in DNA repair. NucS endonuclease, a novel endonuclease recently identified in some HA and bacteria, has been shown to act on branched, mismatched, and deaminated DNA, suggesting that this endonuclease is a multifunctional enzyme involved in NER, MMR, and deaminated base repair in a non-canonical manner. However, the catalytic mechanism and the physiological function of NucS endonucleases from HA need to be further clarified to determine how they participate in the different DNA repair pathways in cells from HA. In this review, we focus on recent advances in our understanding of the function of NucS endonucleases from HA in NER, MMR, and deaminated DNA repair, and propose directions for future studies of the NucS family of endonucleases.

Repair of Hypoxanthine in DNA Revealed by DNA Glycosylases and Endonucleases From Hyperthermophilic Archaea

“…Later, the EndoNucS homologs from the hyperthermophilic euryarchaeon T. kodakarensis and T. gammatolerans, and the hyperthermophilic crenarchaeon Sulfolobus islandius REY15A have been reported, possessing the activity on mismatched and Hx-containing DNA (Ishino et al, 2016;Ahmad et al, 2020;Zhang et al, 2020a). Intriguingly, these three EndoNucS homologs from HA harbor distinct cleavage sites, as reviewed in our recent publication (Zhang et al, 2020b).…”

Biogenesis of DNA-carrying extracellular vesicles by the dominant human gut methanogenic archaeon

“…This result is consistent with EV purification strategy used, where proteinaceous virus particles are not expected to co-float with the lipid-containing membrane vesicles. The top 6 most abundant protein in the EVs is the endonuclease EndoMS/NucS (A5UKH4) ( Table S3 ), a multifunctional enzyme involved in DNA repair processes such as nucleotide excision repair, mismatch repair, and deaminated base repair (Ishino et al, 2016; Zhang et al, 2020). Presumably, EndoMS/NucS is incorporated into EVs along with its damaged DNA substrates.…”

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

“…NRC-1 does not increase the mutation rate [327], suggesting that some archaea may carry more than one active MMR system. EndoMS (also named NucS) is an endonuclease first characterized in vitro in P. abyssi, where it acts on branched DNA structures containing flapped and splayed DNA [328][329][330][331]. EndoMS is present in bacteria of the phylum Actinobacteria and in most members of archaea that lack functional MutSL homologues.…”