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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.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7343888 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhang Likui L Jiang Donghao D Wu Mai M Yang Zhihui Z Oger Philippe M PM

Frontiers in microbiology 20200702

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 protein ...[more]

PMID: 32714287

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Project description:EndoMS is a recently identified mismatch specific endonuclease in Thermococcales of Archaea and Mycobacteria of Bacteria. The homologs of EndoMS are conserved in Archaea and Actinobacteria, where classic MutS-MutL-mediated DNA mismatch repair pathway is absent or non-functional. Here, we report a study on the in vitro mismatch cleavage activity and in vivo function of an EndoMS homolog (SisEndoMS) from Sulfolobus islandicus REY15A, the model archaeon belonging to Crenarchaeota. SisEndoMS is highly active on duplex DNA containing G/T, G/G, and T/T mismatches. Interestingly, the cleavage activity of SisEndoMS is stimulated by the heterotrimeric PCNAs, and when Mn2+ was used as the co-factor instead of Mg2+, SisEndoMS was also active on DNA substrates containing C/T or A/G mismatches, suggesting that the endonuclease activity can be regulated by ion co-factors and accessory proteins. We compared the spontaneous mutation rate of the wild type strain REY15A and ?endoMS by counter selection against 5-fluoroorotic acid (5-FOA). The endoMS knockout mutant had much higher spontaneous mutation rate (5.06 × 10-3) than that of the wild type (4.6 × 10-6). A mutation accumulation analysis also showed that the deletion mutant had a higher mutation occurrence than the wild type, with transition mutation being the dominant, suggesting that SisEndoMS is responsible for mutation avoidance in this hyperthermophilic archaeon. Overexpression of the wild type SisEndoMS in S. islandicus resulted in retarded growth and abnormal cell morphology, similar to strains overexpressing Hje and Hjc, the Holliday junction endonucleases. Transcriptomic analysis revealed that SisEndoMS overexpression led to upregulation of distinct gene including the CRISPR-Cas IIIB system, methyltransferases, and glycosyltransferases, which are mainly localized to specific regions in the chromosome. Collectively, our results support that EndoMS proteins represent a noncanonical DNA repair pathway in Archaea. The mechanism of the mismatch repair pathway in Sulfolobus which have a single chromosome is discussed.

Dataset Information

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

Publications

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

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