Hailey Gahlon


Last Name

Gahlon

First Name

Hailey

ORCID

0000-0003-4388-2798

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2013 - 2019122020 - 20245
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Publications 1 - 10 of 17
  • Structurally altered nucleosides
    Item type: Doctoral Thesis
    Gahlon, Hailey (2013)
  • The mitochondrial DNA common deletion as a potential biomarker of cancer-associated fibroblasts from skin basal and squamous cell carcinomas
    Item type: Journal Article
    Fontana, Gabriele; MacArthur, Michael R.; Rotankova, Nadezhda; et al. (2024)
    Scientific Reports
    Cancer-associated fibroblasts (CAFs) are components of the tumor microenvironment and represent appealing therapeutic targets for translational studies. Conventional protein-based biomarkers for CAFs have been reported to be limited in their specificity, rendering difficult the identification of CAFs from normal fibroblasts (NFs) in clinical samples and dampening the development of CAF-targeted therapies to treat cancer. In this study, we propose the mitochondrial RNA and the mitochondrial DNA (mtDNA) common deletion (CD) as novel indicators of CAF identity. We found that cancer-activation correlated with decreased levels of the mtDNA CD, a condition not due to altered mitochondria count or cellular redox state, but potentially linked to the generalized overexpression of mtDNA maintenance genes in CAFs. Decreased mtDNA CD content in CAFs was associated with moderate to strong overexpression of mtDNA-encoded genes and to slightly improved mitochondrial function. We identified similar patterns of upregulation of mtDNA-encoded genes in independent single-cell RNA seq data obtained from squamous cell carcinoma (SCC) patients. By using the identified nucleic acids-based indicators, identification of CAFs from NFs could be improved, leading to potential therapeutic benefits in advancing translational and clinical studies.
  • Hydrogen-Bonding Interactions at the DNA Terminus Promote Extension from Methylguanine Lesions by Human Extender DNA Polymerase zeta
    Item type: Journal Article
    Räz, Michael H.; Sturla, Shana J.; Gahlon, Hailey (2018)
    Biochemistry
  • O6-Alkylguanine postlesion DNA synthesis is correct with the right complement of hydrogen bonding
    Item type: Journal Article
    Gahlon, Hailey; Boby, Melissa L.; Sturla, Shana J. (2014)
    ACS Chemical Biology
  • Tolerance of Base Pair Size and Shape in Postlesion DNA Synthesis
    Item type: Journal Article
    Gahlon, Hailey; Schweizer, W. Bernd; Sturla, Shana J. (2013)
    Journal of the American Chemical Society
  • Hydrogen Bonding or Stacking Interactions in Differentiating Duplex Stability in Oligonucleotides Containing Synthetic Nucleoside Probes for Alkylated DNA
    Item type: Journal Article
    Gahlon, Hailey; Sturla, Shana J. (2013)
    Chemistry - A European Journal
  • Cryo-EM structures of the eukaryotic replicative helicase bound to a translocation substrate
    Item type: Journal Article
    Ali, Ferdos A.; Renault, Ludovic; Gannon, Julian; et al. (2016)
    Nature Communications
    The Cdc45-MCM-GINS (CMG) helicase unwinds DNA during the elongation step of eukaryotic genome duplication and this process depends on the MCM ATPase function. Whether CMG translocation occurs on single- or double-stranded DNA and how ATP hydrolysis drives DNA unwinding remain open questions. Here we use cryo-electron microscopy to describe two subnanometre resolution structures of the CMG helicase trapped on a DNA fork. In the predominant state, the ring-shaped C-terminal ATPase of MCM is compact and contacts single-stranded DNA, via a set of pre-sensor 1 hairpins that spiral around the translocation substrate. In the second state, the ATPase module is relaxed and apparently substrate free, while DNA intimately contacts the downstream amino-terminal tier of the MCM motor ring. These results, supported by single-molecule FRET measurements, lead us to suggest a replication fork unwinding mechanism whereby the N-terminal and AAA+ tiers of the MCM work in concert to translocate on single-stranded DNA.
  • Absence of nuclease activity in commonly used oxygen-scavenging systems
    Item type: Journal Article
    Gahlon, Hailey; Poudevigne-Durance, Paul; Rueda, David (2017)
    BMC Research Notes
    Objective Oxygen scavenging systems are routinely used during single-molecule imaging experiments to improve fluorescent dye stability. Previous work has shown nuclease contamination in the commonly used oxygen scavenging systems. This study evaluates the potential for nuclease contamination in these oxygen scavenging systems. Results Linear and plasmid DNA was incubated with two different oxygen scavenging systems (1) protocatechuic acid (PCA)-protocatechuate-3,4-dioxygenase (PCD) and (2) glucose-coupled glucose oxidase/catalase (GODCAT). No nucleic acid degradation was observed on single and double-stranded linear DNA and plasmid DNA, indicating the absence of nuclease contamination in these oxygen scavenging systems.
  • A gene-targeted polymerase-mediated strategy to identify O6 -methylguanine damage
    Item type: Journal Article
    Aloisi, Claudia M.N.; Sturla, Shana J.; Gahlon, Hailey (2019)
    Chemical Communications
    Detecting DNA adducts in cancer genes is important for understanding cancer etiology. This study reports a strategy to identify the mutagenic DNA adduct O6-methylguanine in K-Ras. The strategy involves selective replication past a synthetic primer when placed opposite O6-methylguanine. Future work can apply this approach to other cancer-relevant genes.
  • Mechanisms of replication and repair in mitochondrial DNA deletion formation
    Item type: Journal Article
    Fontana, Gabriele A.; Gahlon, Hailey (2020)
    Nucleic Acids Research
    Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.
Publications 1 - 10 of 17