Håvard Homberset

• Barouti, Angeliki; Herfindal, Lars; Vagolu, Siva Krishna; Homberset, Håvard; Tonjum, Tone & Kopplin, Georg [Show all 7 contributors for this article] (2024). Evaluation of the cytotoxic and antimicrobial potential of epiphytic biomass obtained from Laminaria hyperborea biorefinery side-streams. Frontiers in Marine Science. ISSN 2296-7745. 11. doi: 10.3389/fmars.2024.1384136.
• Tapera, Michael; Kekeçmuhammed, Hüseyin; Sahin, Kader; Vagolu, Siva Krishna; Lherbet, Christian & Homberset, Håvard [Show all 12 contributors for this article] (2022). Synthesis, characterization, anti-tuberculosis activity and molecular modeling studies of thiourea derivatives bearing aminoguanidine moiety. Journal of Molecular Structure. ISSN 0022-2860. 1270:133899, p. 1–17. doi: 10.1016/j.molstruc.2022.133899.
• Keleş Atıcı, Rüveyde; Doğan, Şengül Dilem; Gündüz, Miyase Gözde; Vagolu, Siva Krishna; Chebaiki, Melina & Homberset, Håvard [Show all 9 contributors for this article] (2022). Urea derivatives carrying a thiophenylthiazole moiety: Design, synthesis, and evaluation of antitubercular and InhA inhibitory activities. Drug development research (Print). ISSN 0272-4391. 83(6), p. 1292–1304. doi: 10.1002/ddr.21958.
• Welekidan, Letemichael Negash; Yimer, Solomon Abebe; Skjerve, Eystein; Dejene, Tsehaye Asmelash; Homberset, Håvard & Tonjum, Tone [Show all 7 contributors for this article] (2021). Whole Genome Sequencing of Drug Resistant and Drug Susceptible Mycobacterium tuberculosis Isolates From Tigray Region, Ethiopia. Frontiers in Microbiology. ISSN 1664-302X. 12. doi: 10.3389/fmicb.2021.743198. Full text in Research Archive
• Yimer, Solomon Abebe; Kalayou, Shewit; Homberset, Håvard; Birhanu, Alemayehu Godana; Riaz, Tahira & Zegeye, Ephrem Debebe [Show all 11 contributors for this article] (2020). Lineage-specific proteomic signatures in the Mycobacterium tuberculosis complex reveal differential abundance of proteins involved in virulence, DNA repair, CRISPR-Cas, bioenergetics and lipid metabolism. Frontiers in Microbiology. ISSN 1664-302X. 11. doi: 10.3389/fmicb.2020.550760. Full text in Research Archive
• Frye, Stephan Alfons; Beyene, Getachew Tesfaye; Namouchi, Amine; Munoz, Marta Gomez; Homberset, Håvard & Kalayou, Shewit [Show all 9 contributors for this article] (2017). The helicase DinG responds to stress due to DNA double strand breaks. PLOS ONE. ISSN 1932-6203. 12:e0187900(11), p. 1–23. doi: 10.1371/journal.pone.0187900.
• Hovland, Eirik; Beyene, Getachew Tesfaye; Frye, Stephan Alfons; Homberset, Håvard; Balasingham, Seetha & Gomez Munoz, Marta [Show all 9 contributors for this article] (2017). DprA from Neisseria meningitidis: properties and role in natural competence for transformation. Microbiology (Reading). ISSN 1350-0872. 163(7), p. 1016–1029. doi: 10.1099/mic.0.000489. Show summary

  DNA processing chain A (DprA) is a DNA-binding protein that is ubiquitous in bacteria and expressed in some archaea. DprA is active in many bacterial species that are competent for transformation of DNA, but its role in Neisseriameningitidis (Nm) is not well characterized. An Nm mutant lacking DprA was constructed, and the phenotypes of the wild-type and ΔdprA mutant were compared. The salient feature of the phenotype of dprA null cells is the total lack of competence for genetic transformation shown by all of the donor DNA substrates tested in this study. Here, Nm wild-type and dprA null cells appeared to be equally resistant to genotoxic stress. The gene encoding DprANm was cloned and overexpressed, and the biological activities of DprANm were further investigated. DprANm binds ssDNA more strongly than dsDNA, but lacks DNA uptake sequence-specific DNA binding. DprANm dimerization and interaction with the C-terminal part of the single-stranded binding protein SSBNmwere demonstrated. dprA is co-expressed with smg, a downstream gene of unknown function, and the gene encoding topoisomerase 1, topA.

• Beyene, Getachew Tesfaye; Balasingham, Seetha; Frye, Stephan Alfons; Namouchi, Amine; Homberset, Håvard & Kalayou, Shewit [Show all 8 contributors for this article] (2016). Characterization of the Neisseria meningitidis Helicase RecG. PLOS ONE. ISSN 1932-6203. 11:e0164588(10), p. 1–31. doi: 10.1371/journal.pone.0164588. Show summary

  Neisseria meningitidis (Nm) is a Gram-negative oral commensal that opportunistically can cause septicaemia and/or meningitis. Here, we overexpressed, purified and characterized the Nm DNA repair/recombination helicase RecG (RecGNm) and examined its role during genotoxic stress. RecGNm possessed ATP-dependent DNA binding and unwinding activities in vitro on a variety of DNA model substrates including a Holliday junction (HJ). Database searching of the Nm genomes identified 49 single nucleotide polymorphisms (SNPs) in the recGNm including 37 non-synonymous SNPs (nsSNPs), and 7 of the nsSNPs were located in the codons for conserved active site residues of RecGNm. A transient reduction in transformation of DNA was observed in the Nm ΔrecG strain as compared to the wildtype. The gene encoding recGNm also contained an unusually high number of the DNA uptake sequence (DUS) that facilitate transformation in neisserial species. The differentially abundant protein profiles of the Nm wildtype and ΔrecG strains suggest that expression of RecGNm might be linked to expression of other proteins involved in DNA repair, recombination and replication, pilus biogenesis, glycan biosynthesis and ribosomal activity. This might explain the growth defect that was observed in the Nm ΔrecG null mutant.

• Frye, Stephan Alfons; Lång, Emma Helena; Beyene, Getachew Tesfaye; Balasingham, Seetha; Homberset, Håvard & Rowe, Alexander D. [Show all 8 contributors for this article] (2015). The Inner Membrane Protein PilG Interacts with DNA and the Secretin PilQ in Transformation. PLOS ONE. ISSN 1932-6203. 10:e0134954(8), p. 1–25. doi: 10.1371/journal.pone.0134954.
• Zegeye, Ephrem Debebe; Balasingham, Seetha ; Lærdahl, Jon Kristen; Homberset, Håvard; Kristiansen, Per Eugen & Tønjum, Tone (2014). Effects of conserved residues and naturally occurring mutations on Mycobacterium tuberculosis RecG helicase activity. Microbiology (Reading). ISSN 1350-0872. 160(1), p. 217–227. doi: 10.1099/mic.0.072140-0. Show summary

  RecG is a helicase that is conserved in nearly all bacterial species. The prototypical Escherichia coli RecG promotes regression of stalled replication forks, participates in DNA recombination and DNA repair, and prevents aberrant replication. Mycobacterium tuberculosis RecG (RecGMtb) is a DNA-dependent ATPase that unwinds a variety of DNA substrates, although its preferred substrate is a Holliday junction. Here, we performed site-directed mutagenesis of selected residues in the wedge domain and motifs Q, I, Ib and VI of RecGMtb. Three of the 10 substitution mutations engineered were detected previously as naturally occurring SNPs in the gene encoding RecGMtb. Alanine substitution mutations at residues Q292, F286, K321 and R627 abolished the RecGMtb unwinding activity, whilst RecGMtb F99A, P285S and T408A mutants exhibited ~25-50 % lower unwinding activity than WT. We also found that RecGMtb bound ATP in the absence of a DNA cofactor.

• Zegeye, Ephrem Debebe; Balasingham, Seetha ; Lærdahl, Jon Kristen; Homberset, Håvard & Tønjum, Tone (2012). Mycobacterium tuberculosis RecG binds and unwinds model DNA substrates with a preference for Holliday junctions. Microbiology (Reading). ISSN 1350-0872. 158(Pt 8), p. 1982–1993. doi: 10.1099/mic.0.058693-0.
• Balasingham, Seetha ; Zegeye, Ephrem Debebe; Homberset, Håvard; Rossi, Marie; Lærdahl, Jon Kristen & Bohr, Vilhelm A. [Show all 7 contributors for this article] (2012). Enzymatic Activities and DNA Substrate Specificity of Mycobacterium tuberculosis DNA Helicase XPB. PLOS ONE. ISSN 1932-6203. 7(5). doi: 10.1371/journal.pone.0036960.
• Tibballs, Katrina Louise Bø; Ambur, Ole Herman; Alfsnes, Kristian; Homberset, Håvard; Frye, Stephan Alfons & Davidsen, Tonje [Show all 7 contributors for this article] (2009). Characterization of the meningococcal DNA glycosylase Fpg involved in base excision repair. BMC Microbiology. ISSN 1471-2180. 9. doi: 10.1186/1471-2180-9-7.
• Lång, Emma Helena; Haugen, Kristine; Fleckenstein, Burkhard; Homberset, Håvard; Frye, Stephan Alfons & Ambur, Ole Herman [Show all 7 contributors for this article] (2009). Identification of neisserial DNA binding components. Microbiology (Reading). ISSN 1350-0872. 155, p. 852–862. doi: 10.1099/mic.0.022640-0.
• Balasingham, Seetha; Collins, RF; Assalkhou, Reza; Homberset, Håvard; Frye, Stephan Alfons & Derrick, JP [Show all 7 contributors for this article] (2007). Interactions between the lipoprotein PilP and the secretin PilQ in Neisseria meningitidis. Journal of Bacteriology. ISSN 0021-9193. 189, p. 5716–5727. doi: 10.1128/JB.00060-07.
• Golovanov, AP; Balasingham, Seetha; Tzitzilonis, C; Goult, B; Lian, L-Y & Homberset, Håvard [Show all 8 contributors for this article] (2006). The Solution Structure of a Domain Neisseria meningitidis Lipoprotein Reveals a New β-Sandwich Fold. Journal of Molecular Biology (JMB). ISSN 0022-2836. 364(2), p. 186–195. doi: 10.1016/j.jmb.2006.08.078.
• Golovanov, Alexander P.; Balasingham, Seetha; Tzitzilonis, Christos; Goult, Benjamin; Lian, Lu-Yun & Homberset, Håvard [Show all 8 contributors for this article] (2006). Assignment of 1H, 13C, and 15N resonance for the PilPpilot protein from Neisseria meningitidis. Journal of Biomolecular NMR. ISSN 0925-2738. 36, p. 68–68.

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• Tonjum, Tone; Homberset, Håvard; Eriksson, Jens & kussell, edo (2018). Update on neisserial transformation . Show summary

  The pathogenic Neisseria species, N. meningitidis and N. gonorrhoeae are readily transformed in vitro by exogenous heterologous DNA, such as antibiotic resistance cassettes. The closely related and generally harmless commensal species N. lactamica (Nla) is less tolerant of DNA heterology and has previously not been described to be competent for natural transformation. A possible explanation for this observation is that Nla-specific restriction endonucleases limit the transformability of Nla. Here, we provide evidence to support this hypothesis, including bioinformatics data consistent with the presence of an abundance of restriction-modification (RM) systems in Nla. Bioinformatics studies also demonstrated an aberrantly low frequency of the restriction/modification site CATG in the Nla genome, which can be attributed to restriction site avoidance. Furthermore, inactivation of genes encoding selected endonucleases increased the efficiency of Nla transformation with heterologous DNA. These results suggest that engineered Nla strains in which one or more RM systems are inactivated could be useful tools for developing anti-microbial vaccines.

• Frye, Stephan Alfons; Balasingham, Seetha; Beyene, Getachew Tesfaye; Homberset, Håvard; Namouchi, Amine & Tonjum, Tone (2016). Meningococcal DNA binding and unwinding proteins. Show summary

  Background: DNA helicases are a ubiquitous group of enzymes that use the energy of nucleoside triphosphate (dNTP) hydrolysis to catalyze the separation of double-stranded DNA (dsDNA). Helicases are involved in essentially every step in DNA metabolism, including replication, DNA repair, recombination, transcription, Holliday junction movement, and displacement of proteins from DNA. We investigated the DNA helicases RecG and DinG from Neisseria meningitidis (NmRecG and NmDinG) and their roles during genotoxic stress, including DNA damage. These helicases belong to superfamily 2, are ATP dependent and exert 5′to 3′ directionality. Our aim was to define the potential roles of NmRecG and NmDinG in DNA repair, recombination and replication (3R). Methods and results: Cell lysates from Nm wildtype and recG and dinG null mutants (NmrecG and dinG) were assessed by quantitative mass spectrometry (MS). In the ∆recG mutant, 16 proteins were differentially expressed as compared to the Nm wildtype. RecN, Ssb and DnaX were upregulated in the Nm∆recG mutant, while the type 4 pilus structural subunit protein PilE as well as pilus biogenesis components (PilF, PilT and PilQ) were downregulated. Global proteomics analysis of Nm wildtype and ∆recG mutant strains thus revealed the most abundant differentially expressed proteins and linked RecG to DNA repair, recombination and replication, pilus biogenesis components and glycan biosynthesis. Notably, when NmdinG cells grown under mitomycin C (MMC) stress, 134 proteins were shown to be differentially abundant compared to the unstressed NmdinG. Most of them are involved in metabolic functions like carbon, amino acid and nucleotide synthesis. Among 3R proteins, polymerase III subunits and recombinational repair proteins RuvA, RuvB, RecB and RecD were significantly downregulated while TopA and SSB were upregulated under stress. Genotoxic stress analysis demonstrated that NmdinG was more sensitive to double-strand DNA breaks (DSB) induced MMC than the Nm wildtype, defining the role of neisserial DinG in DSB repair. An unusually high number of DNA uptake sequences (DUS) that facilitate the transformation in neisserial species were identified in the Nm recG gene, signifying its importance. The genes encoding NmRecG and NmDinG were cloned and overexpressed, the recombinant NmRecG and NmDinG proteins were purified to homogeneity and their enzymatic activity was characterized. NmRecG acts through its ability to process Holliday junction (HJ) intermediates and catalyse branch migration of complex DNA structures. NmRecG and NmDinG possess 5′to3′ directionality and prefer DNA substrates containing a 5′overhang. ATPase activity of NmRecG and NmDinG is strictly DNA-dependent, and DNA unwinding activity requires nucleoside triphosphate in addition to divalent metal cations. This study contributes to understand the overall role of RecG in neisserial genome maintenance and evolution. Conclusions: This study gives new insight into the functional roles and interactions of the helicases RecG and DinG, elucidation their roles in meningococcal DNA repair and recombination, with a link of RecG to transformation also through pilus biogenesis.

• Zegeye, Ephrem Debebe; Balasingham, Seetha ; Lærdahl, Jon Kristen; Homberset, Håvard & Tønjum, Tone (2013). Mycobacterium tuberculosis RecG is a helicase enzyme with broad DNA substrate specificity.
• Balasingham, Seetha ; Zegeye, Ephrem Debebe; Homberset, Håvard; Rossi, Marie; Lærdahl, Jon Kristen & Bohr, Vilhelm A. [Show all 7 contributors for this article] (2013). Unique features of DNA repair helicases in Mycobacterium tuberculosis.
• Balasingham, Seetha ; Zegeye, Ephrem Debebe; Homberset, Håvard; Rossi, Marie; Lærdahl, Jon Kristen & Bohr, Vilhelm A. [Show all 7 contributors for this article] (2013). Unique Features of DNA Helicases in Mycobacterium tuberculosis.
• Zegeye, Ephrem Debebe; Balasingham, Seetha ; Lærdahl, Jon Kristen; Homberset, Håvard & Tønjum, Tone (2013). Mycobacterium tuberculosis RecG is a helicase enzyme with broad DNA substrate specificity.
• Beyene, Getachew Tesfaye; Balasingham, Seetha ; Homberset, Håvard & Tønjum, Tone (2013). The helicase RecG in Neisseria meningitidis influences transformation efficiency.
• Zegeye, Ephrem Debebe; Balasingham, Seetha ; Lærdahl, Jon Kristen; Homberset, Håvard & Tønjum, Tone (2012). Mycobacterium tuberculosis RecG is a helicase enzyme with diverse DNA substrate affinities.
• Balasingham, Seetha ; Zegeye, Ephrem Debebe; Nilsen, Mariann; Homberset, Håvard; Rossie, Marie & Lærdahl, Jon Kristen [Show all 8 contributors for this article] (2012). Delineating the functions of DNA repair helicases in Mycobacterium tuberculosis.
• Zegeye, Ephrem Debebe; Balasingham, Seetha ; Lærdahl, Jon Kristen; Homberset, Håvard & Tønjum, Tone (2012). Mycobacterium tuberculosis RecG is a helicase enzyme with diverse DNA substrate affinities.
• Balasingham, Seetha ; Zegeye, Ephrem Debebe; Nilsen, Mariann; Homberset, Håvard; Rossie, Marie & Laerdahl, Jon K [Show all 8 contributors for this article] (2012). Delineating the functions of DNA repair helicases in Mycobacterium tuberculosis.
• Hovland, Eirik; Frye, Stephan Alfons; Homberset, Håvard; Tønjum, Tone & Ambur, Ole Herman (2010). The role of DprA in neisserial transformation.
• Ambur, Ole Herman; Alfsnes, Kristian; Hovland, Eirik; Homberset, Håvard; Lærdahl, Jon Kristen & Frye, Stephan Alfons [Show all 9 contributors for this article] (2010). Mechanisms of neisserial transformation and the evolution of sexual reproduction.
• Lång, Emma; Fleckenstein, Burkhard; Homberset, Håvard; Frye, Stephan Alfons; Haugen, Kristine & Ambur, Ole Herman [Show all 7 contributors for this article] (2008). Identification of novel DNA binding proteins in Neisseria meningitidis.
• Frye, Stephan Alfons; Ambur, Ole Herman; Tønjum, Tone; Balasingham, Seetha ; Lång, Emma & Alfsnes, Kristian [Show all 9 contributors for this article] (2007). News on DUS.
• Balasingham, Seetha; Collins, Richard F.; Assalkhou, Reza; Frye, Stephan Alfons; Homberset, Håvard & Golovanov, Alexander P. [Show all 9 contributors for this article] (2006). Meningococcal lipoprotein PilP: its structure and role in pilus biogenesis and transformation.
• Frye, Stephan Alfons; Collins, R; Assalkhou, Reza; Balasingham, Seetha; Lång, Emma Helena & Homberset, Håvard [Show all 9 contributors for this article] (2006). MENINGOCOCCAL DNA UPTAKE IS COUPLED TO PILUS RETRACTION.
• Balasingham, Seetha ; Frye, Stephan Alfons; Assalkhou, Reza; Ambur, Ole Herman; Collins, Richard F. & Homberset, Håvard [Show all 10 contributors for this article] (2006). Meningococcal transformation and DNA binding components.
• Frye, Stephan Alfons; Balasingham, Seetha ; Assalkhou, Reza; Homberset, Håvard; Collins, Richard F. & Derrick, Jeremy P. [Show all 7 contributors for this article] (2006). Meningococcal secretin PilQ: Actions and Interactions.
• Balasingham, Seetha ; Assalkhou, Reza; Frye, Stephan Alfons; Collins, Richard F.; Golovanov, Alexander P. & Homberset, Håvard [Show all 8 contributors for this article] (2006). Meningococcal lipoprotein PilP directly interacts with the secretin PilQ and DNA.
• Frye, Stephan Alfons; Davidsen, Tonje; Assalkhou, Reza; Balasingham, Seetha; Ambur, Ole Herman & Tuven, Hanne [Show all 10 contributors for this article] (2005). Meningococcal genome instability and pathogenesis.
• Frye, Stephan Alfons; Assalkhou, Reza; Balasingham, Seetha ; Tuven, Hanne Kim; Vahdani-Benam, Afsaneh & Homberset, Håvard [Show all 7 contributors for this article] (2004). The meningococcal secretin PilQ: Actions and Interactions.
• Frye, Stephan Alfons; Assalkhou, Reza; Balasingham, Seetha; Tuven, Hanne; Benam, Afsaneh V & Homberset, Håvard [Show all 7 contributors for this article] (2004). The meningococcal secretin PilQ: Actions and interactions.

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