Mechanistic insights into Lhr helicase function in DNA repair

Buckley, Ryan J.; Kramm, Kevin; Cooper, C.D.O.; Grohmann, Dina; Bolt, Edward L.

doi:10.1042/bcj20200379

Cited by 11 publications

(37 citation statements)

References 36 publications

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“…We determined that it is a monomeric DNA/RNA helicase able to process DNA:RNA and RNA:RNA duplexes. Moreover, for other archaeal aLhr helicases that were proposed to be DNA helicases involved in DNA repair and recombination [15,41], it was unclear if they belong to the same aLhr2 group. It also interrogated the relationship that exists between the archaeal and bacterial Lhr proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, only four out of 219 have lost both genes. We defined that the characterized Lhr proteins of S. solfataricus, S. acidocaldarius, and M. thermautotrophicus [15,16] belong to the aLhr2 group. To date, no aLhr1 were characterized.…”

Section: Discussionmentioning

confidence: 99%

“…While, both proteins have similar binding affinities for nucleic acids and do not show any specificity for DNA50 substrates (Table 1), their activities differ because of their respective substrates and unwinding velocities. Therefore, Hel308 and aLhr2 that were previously reported to be involved in DNA repair [15,40] most likely operate to perform different tasks in DNA transactions.…”

Section: Tbar-alhr2 Is a Nucleic Acid Binding Protein With Similar Afmentioning

confidence: 99%

“…aLhr1 has an additional cysteine-rich motif at its C-terminal end. Only few Lhr from Sulfolobales (TACK) and Methanobacteriales (Euryarchaea) have been studied [15,16]. Lhr of Sulfolobus islandicus (SiRe_1605) was found to be important for the transcription of genes in nucleotide metabolism and DNA repair [17].…”

Section: Introductionmentioning

confidence: 99%

“…In vitro, Lhr of Methanothermobacter thermautotrophicus (Mthe) was also found to have a 3′-5′ directional DNA translocase ac-tivity and to act on forked DNA structures. In a genetic assay, its expression gave a phenotype identical to the DNA helicases Hel308 and RecQ involved in replication-coupled DNA repair [15]. In addition, aLhr2 of Pyrococcus abyssi (Paby) was detected in the interaction network of proteins implicated in DNA replication and repair [19].…”

Section: Introductionmentioning

confidence: 99%

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Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase

Hajj¹,

Langendijk-Genevaux²,

Batista³

et al. 2021

Preprint

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Helicases are proteins that use the energy of ATP to unwind nucleic acids and to remodel protein-nucleic acid complexes. They are involved in almost every aspect of the DNA and RNA metabolisms and participate in numerous repair mechanisms that maintain cellular integrity. Helicases are classified into 6 superfamilies (SF1-6). The archaeal Lhr-type proteins are SF2 helicases that are mostly uncharacterized. They have been proposed to be a DNA helicase that acts in DNA recombination and repair processes in Sulfolobales and Methanothermobacter. In parallel, a protein annotated as an Lhr2 protein was also found in the network of proteins involved in RNA metabolism in Thermococcales. To this respect, we performed in-depth phylogenomic analyses to report the classification and taxonomic distribution of Lhr-type proteins in Archaea, and to better understand their relationship with bacterial Lhr. Furthermore, with the goal of envisioning the role(s) of aLhr2 in archaeal cells, we deciphered the enzymatic activities of aLhr2 from Thermococcus barophilus (Tbar). We showed that Tbar-aLhr2 is a DNA/RNA helicase acting on DNA:RNA and RNA:RNA duplexes and proposed that aLhr2 helicases are involved in processes dependent of DNA and RNA transactions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Tbar-alhr2 Is a Nucleic Acid Binding Protein With Similar Afmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase

Hajj¹,

Langendijk-Genevaux²,

Batista³

et al. 2021

Preprint

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Clinically relevant mutations in regulatory regions of metabolic genes facilitate early adaptation to ciprofloxacin in Escherichia coli

Pal,

Ghosh,

Thakur

et al. 2024

Nucleic Acids Research

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The genomic landscape associated with early adaptation to ciprofloxacin is poorly understood. Although the interplay between core metabolism and antimicrobial resistance is being increasingly recognized, mutations in metabolic genes and their biological role remain elusive. Here, we exposed Escherichia coli to increasing gradients of ciprofloxacin with intermittent transfer-bottlenecking and identified mutations in three non-canonical targets linked to metabolism including a deletion (tRNA-ArgΔ414-bp) and point mutations in the regulatory regions of argI (ARG box) and narU. Our findings suggest that these mutations modulate arginine and carbohydrate metabolism, facilitate anaerobiosis and increased ATP production during ciprofloxacin stress. Furthermore, mutations in the regulatory regions of argI and narU were detected in over 70% of sequences from clinical E. coli isolates and were overrepresented among ciprofloxacin-resistant isolates. In sum, we have identified clinically relevant mutations in the regulatory regions of metabolic genes as a central theme that drives physiological changes necessary for adaptation to ciprofloxacin stress.

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Escherichia coliDNA repair helicase Lhr is also a uracil‐DNA glycosylase

Buckley,

Lou‐Hing,

Hanson

et al. 2023

Molecular Microbiology

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DNA glycosylases protect genetic fidelity during DNA replication by removing potentially mutagenic chemically damaged DNA bases. Bacterial Lhr proteins are well‐characterized DNA repair helicases that are fused to additional 600–700 amino acids of unknown function, but with structural homology to SecB chaperones and AlkZ DNA glycosylases. Here, we identify that Escherichia coli Lhr is a uracil‐DNA glycosylase (UDG) that depends on an active site aspartic acid residue. We show that the Lhr DNA helicase activity is functionally independent of the UDG activity, but that the helicase domains are required for fully active UDG activity. Consistent with UDG activity, deletion of lhr from the E. coli chromosome sensitized cells to oxidative stress that triggers cytosine deamination to uracil. The ability of Lhr to translocate single‐stranded DNA and remove uracil bases suggests a surveillance role to seek and remove potentially mutagenic base changes during replication stress.

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Mechanistic insights into Lhr helicase function in DNA repair

Cited by 11 publications

References 36 publications

Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase

Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase

Clinically relevant mutations in regulatory regions of metabolic genes facilitate early adaptation to ciprofloxacin in Escherichia coli

Escherichia coliDNA repair helicase Lhr is also a uracil‐DNA glycosylase

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