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Articles 481 - 510 of 7399

Full-Text Articles in Cell and Developmental Biology

Neuronal Cftr: A Study Of Subcellular Localization And Interactions With Implications For A Role In Synaptic Transmission, Brandon J. Leviskas Apr 2025

Neuronal Cftr: A Study Of Subcellular Localization And Interactions With Implications For A Role In Synaptic Transmission, Brandon J. Leviskas

LSU Doctoral Dissertations

Protein-protein interactions vary among cell types and the localization of these interactions help to define protein function. The function of cystic fibrosis transmembrane conductance regulator (CFTR) is well established in the context of epithelial tissue due to the debilitating effects of its mutations that cause the disease cystic fibrosis. While in neurons a role has been established in our lab for CFTR in the regulation of cytosolic Cl- in retinal amacrine cells (ACs). This research sets out to learn if CFTR has a synaptic role. Exploring this potential role, localization of CFTR was examined using fluorescent and immunogold labeled transmission …


Robust Sex Determination In The Caenorhabditis Nigoni Germ Line, Jonathan P Harbin, Yongquan Shen, Shin-Yi Lin, Kevin Kemper, Eric S Haag, Erich M Schwarz, Ronald E Ellis Apr 2025

Robust Sex Determination In The Caenorhabditis Nigoni Germ Line, Jonathan P Harbin, Yongquan Shen, Shin-Yi Lin, Kevin Kemper, Eric S Haag, Erich M Schwarz, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sexual characteristics and reproductive systems are dynamic traits in many taxa, but the developmental modifications that allow change and innovation are largely unknown. A leading model for this process is the evolution of self-fertile hermaphrodites from male/female ancestors. However, these studies require direct analysis of sex-determination in male/female species, as well as in the hermaphroditic species that are related to them. In Caenorhabditis nematodes this has only become possible recently, with the discovery of new species. Here, we use gene editing to characterize major sex-determination genes in C. nigoni, a sister to the widely studied hermaphroditic species C. briggsae. These …


Leveraging Attention Mechanism To Unlock Gene And Protein Attributes, Ala Jararweh Apr 2025

Leveraging Attention Mechanism To Unlock Gene And Protein Attributes, Ala Jararweh

Computer Science ETDs

Advancing personalized medicine depends on effectively integrating and interpreting the vast, heterogeneous landscape of biological data, from genomic sequences and transcriptomics to the insights embedded in scientific literature. Current machine learning models often focus on single data modalities, limiting their capacity to capture the multifaceted nature of biological systems. We address this gap by developing three attention-based machine-learning models integrating diverse data modalities. Firstly, DeepVul is a multi-task model that leverages cancer transcriptome data to predict genes critical for cancer survival and their corresponding drugs. Subsequently, LitGene refines gene representations by integrating textual information from the scientific literature. Finally, Protein2Text …


Biology Department Publications: 2024, Sam Lindgren Apr 2025

Biology Department Publications: 2024, Sam Lindgren

Biology Department Bibliographies

This document is a non-comprehensive list of publications made by graduate students, post-doctoral researchers, and faculty members in the Biology Department in 2024. It indexes those publications available through PubMed, and serves as an archival record of the Department's robust scholarly contributions.


The Impact Of Paternal Obesity On Placental Development And Function During Pregnancy, Delaney G. Wolfe, Delaney G. Wiolfe Apr 2025

The Impact Of Paternal Obesity On Placental Development And Function During Pregnancy, Delaney G. Wolfe, Delaney G. Wiolfe

Department of Nutrition Student Projects

Paternal obesity is a rising concern in conception and reproductive health, with increasing evidence suggesting its impact on pregnancy outcomes. While maternal obesity's effects on fetal development and placental function are well-documented, the role of paternal obesity remains less understood. The placenta, crucial for nutrient exchange and fetal development, can be disrupted by inflammation, oxidative stress, and epigenetic modifications, potentially leading to long-term health implications for both maternal and fetal health. Understanding the paternal influence on placental development is essential for improving pregnancy outcomes and offspring
health. This study aims to investigate the relationship between paternal obesity on placental function …


Solving The Structure Of An Ancestral Protein Tyrosine Phosphatase, Natalie Turcsanski, Edna Armah Apr 2025

Solving The Structure Of An Ancestral Protein Tyrosine Phosphatase, Natalie Turcsanski, Edna Armah

Student Research Symposium

Protein tyrosine phosphatases (PTPs) regulate cell signaling by removing phosphate groups from tyrosine residues. Malfunction of these enzymes can lead to diseases such as diabetes and cancer. A conserved feature among PTPs is the catalytic acid loop, essential for phosphate removal. Computational analysis of PTP structures revealed that ancestral PTPs have considerable variation in conformations of this loop, sparking interest in their further study. The Asgard group, identified as ancestral to eukaryotic PTPs, was successfully expressed and purified under optimized conditions. Current efforts focus on optimizing crystallization to obtain larger crystals for structural analysis. This project will investigate the allosteric …


Understanding Challenges To Breast Cancer Screening For African American Women In Detroit: A Study Of Social And Healthcare Inequities, Miranda Goodson, Whitney Bowyer, Erika Lopez, Anna Lundh Apr 2025

Understanding Challenges To Breast Cancer Screening For African American Women In Detroit: A Study Of Social And Healthcare Inequities, Miranda Goodson, Whitney Bowyer, Erika Lopez, Anna Lundh

Medical Student Research Symposium

African American (AA) women have lower adherence to breast cancer screening guidelines, which may contribute to delayed diagnoses and reduced survival rates. These disparities are often influenced by limited access to quality healthcare and persistent inequities faced within Michigan. With Detroit's population being 77% AA, examining studies focused on the experiences of Black women within urban healthcare networks is essential to understanding the connections between demographic, socioeconomic factors, and breast cancer outcomes. To assess these studies, a literature search was conducted using Ovid Medline yielding 24 associated articles.

Mammogram rates among AA women in Detroit remain low, reflecting a complex …


Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo Apr 2025

Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo

Medical Student Research Symposium

Endometrial cancer is rising in incidence in the United States, notably among premenopausal women. This increase and the trend of delayed childbearing warrant the need for further advancement in fertility-sparing treatment for endometrial cancer. A gene left widely unexplored in its possible clinical utility as a target for fertility-sparing treatment is KMT2D, a lysine-specific methyltransferase and tumor suppressor. Preliminary gene set enrichment analysis on a 12Z endometriotic epithelial cell line identified TIMP3 as a gene that is possibly regulated by KMT2D expression. TIMP3 encodes an irreversible inhibitor of matrix metalloproteinases (MMPs), a well-recognized class of proteins as contributing to the …


Cytokinesis & Dbf2, Katharine Gray, Katie Shannon Apr 2025

Cytokinesis & Dbf2, Katharine Gray, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.


Discovering Localization Of Fun19 Orf In Yeast, Megan Percy, Galayna Baur, Katie Shannon Apr 2025

Discovering Localization Of Fun19 Orf In Yeast, Megan Percy, Galayna Baur, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.


The Effects Of Preventing Dephosphorylation Of Iqg1 On Cytokinesis, Jenna L. Mueller, Katie Shannon Apr 2025

The Effects Of Preventing Dephosphorylation Of Iqg1 On Cytokinesis, Jenna L. Mueller, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.


Characterization Of An Iqg1 Phosphorylation Mutant, Lindsay Scheider, Alexis Ham, Katie Shannon Apr 2025

Characterization Of An Iqg1 Phosphorylation Mutant, Lindsay Scheider, Alexis Ham, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.


Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie Apr 2025

Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie

LSU Doctoral Dissertations

Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …


Adipocyte-Derived Cchamide-1, Eiger, Growth-Blocking Peptide 3, And Unpaired 2 Regulate Drosophila Melanogaster Oogenesis, Chad Simmons, Isaiah Williams, Tancia Bradshaw, Alissa R. Armstrong Apr 2025

Adipocyte-Derived Cchamide-1, Eiger, Growth-Blocking Peptide 3, And Unpaired 2 Regulate Drosophila Melanogaster Oogenesis, Chad Simmons, Isaiah Williams, Tancia Bradshaw, Alissa R. Armstrong

Faculty Publications

In addition to energy storage, adipose tissue communication to other organs plays a key role in regulating organismal physiology. While the link between adipose tissue dysfunction and pathophysiology, including diabetes, chronic inflammation, and infertility, is clear, the molecular mechanisms that underlie these associations have not been fully described. We use Drosophila melanogaster as a model to better understand how adipose tissue communicates to the ovary. In this study, we utilized D. melanogaster’s robust genetic toolkit to examine the role of five adipokines known to control larval growth during development, CCHamide-1, CCHamide-2, eiger, Growth-blocking peptide 3, and unpaired 2 in regulating …


Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden Apr 2025

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …


College Of Natural Sciences Newsletter, Spring 2025, College Of Natural Sciences Apr 2025

College Of Natural Sciences Newsletter, Spring 2025, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message from Dr. Sen Subramanian
Page 2 Student Spotlights
Page 3 Kaushik honored, Three-Minute Thesis, & Ice Cores revealed
Page 4 Alumni Spotlight
Page 5 Day of Scholars
Page 6 Cyanide research, Record Research Expenditures, Adhikari awarded Miller Research Award
Page 8 Hanson Receives NSF Grant
Page 9 Snow Lab Research Team
Page 10 Faculty Awards
Page 11 Drone Day
Page 13 Khalaf Awarded Presidential Award


Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes Apr 2025

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …


Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr. Apr 2025

Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …


Focal Adhesion Genes And Proteins Are Differentially Expressed Across Cell Types In Down Syndrome, Brian Yoon Apr 2025

Focal Adhesion Genes And Proteins Are Differentially Expressed Across Cell Types In Down Syndrome, Brian Yoon

Senior Theses

Down syndrome (DS), caused by an extra copy of chromosome 21, leads to widespread gene expression changes through mechanisms such as transcriptional dysregulation and altered protein interactions. These disruptions contribute to a range of clinical features, including impaired wound healing, immune dysfunction, and neurodevelopmental abnormalities. This study focused on how DS affects fibroblast morphology and motility—processes critical for tissue repair and brain development. Using quantitative immunocytochemistry and image analysis, we found that DS fibroblasts displayed a broader, less polarized shape, with increased cell perimeter and reduced aspect ratio. However, levels of key adhesion proteins like vinculin, FAK, and β-actin were …


Therapeutic Role Of Bioactive Peptides Derived From Hemoglobin, Priya Antony Pereppadan Apr 2025

Therapeutic Role Of Bioactive Peptides Derived From Hemoglobin, Priya Antony Pereppadan

Dissertations

Bioactive peptides are peptide fragments derived from the proteolytic cleavage or maturation of functional proteins that have shown promising therapeutic potential in addressing major health challenges, including type 2 diabetes, hypertension, and pain management. Diabetes is characterized by high blood glucose levels due to insufficient insulin production or utilization. There are several therapeutic targets for managing diabetes, and one key target is dipeptidyl peptidase IV (DPP IV) due to its role in glucose metabolism. In hypertension, angiotensin-converting enzyme 1 (ACE1) is critical for regulating blood pressure by forming angiotensin II, and its inhibition represents an established treatment strategy. Additionally, the …


Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr Mar 2025

Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

This project aims to create CRISPR-CAS9 mutations in the APETELA3 (AP3) gene of the model plant Arabidopsis thaliana. AP3 is a class B gene critical to the petal and stamen development of Arabidopsis flowers. AP3 is defined in a MADS domain, which binds directly to DNA and may be responsible for the expression of the CaRG-box genes. AP3 works in conjunction with PISTILLATA (PI), AGAMOUS (AG), APETALA1 (AP1), and SEPALLATA (SEP) genes to specify the development in the second and third whorls of the flower. While several alleles of AP3 already exist, these alleles are strong alleles that knockout gene …


Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew Mar 2025

Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

No abstract provided.


Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel Mar 2025

Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel

USF Tampa Graduate Theses and Dissertations

Neurodegenerative diseases often feature the pathological buildup of misfolded proteins, and tau is a principal culprit in multiple tauopathies. One chaperone of emerging interest is DnaJB6b, a member of the Hsp40/DnaJ family, which exhibits potent anti-aggregation activity against several disease-related proteins. Recent investigations highlight its unique capacity to recognize and neutralize aggregation-prone forms of tau. DnaJB6b appears potent against multiple variants of tau and may be acting against tau, in part, by directing misfolded tau toward proteasomal clearance. The first lines of evidence come from systematic chaperone screens, where DnaJB6b repeatedly emerged as a strong suppressor of tau seeding. Further …


Studies On Cell Cycle Regulation And Ecm Modification During Tubular Organ Formation In Drosophila Embryos, Jeffrey Matthew Mar 2025

Studies On Cell Cycle Regulation And Ecm Modification During Tubular Organ Formation In Drosophila Embryos, Jeffrey Matthew

LSU Doctoral Dissertations

The formation of tubular organs—such as the heart and kidneys—is a complex developmental process that requires the precise coordination of tissue remodeling with dynamic changes in cellular behavior. Key processes including cell proliferation, apoptosis, and extracellular matrix (ECM) formation must be tightly synchronized with mechanisms that generate and transmit physical forces, transforming a flat epithelial sheet into a three-dimensional organ. Disruptions in the homeostasis of these processes during organogenesis can lead to congenital defects, such as pulmonary atresia and renal hypoplasia.

To investigate the mechanisms underlying epithelial morphogenesis, the Chung laboratory employs the Drosophila embryonic salivary gland (SG) as a …


College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences Mar 2025

College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 2 Dean's Message
Page 3 Department Highlights
Page 4 One Day for State
Page 5 New Students in Wecota
Page 6-8 Faculty Excellence
Page 9 SDSU Physics Students Recognized
Page 9 Prairie Doc Watch Party
Page 10-11 Student Excellence
Page 11 Connections Abroad
Page 12-13 CNS’s Research Centers
Page 14 Connections Abroad
Page 14 Dean Wolf-Hall Retired
Page 15 Outreach Program
Page 15 Events and Traditions
Page 16 Student Spotlight
Page 17 Alumni Spotlight
Page 18-19 SDSU Alum at Paris Paralympics
Page 20 Work Anniversaries & Programs


The Mechanistic Target Of Rapamycin Mediates Clostridium Perfringens-Induced Chicken Necrotic Enteritis Attenuated By Secondary Bile Acid Deoxycholic Acid, Mohit Bansal, Tahrir Alenezi, Ying Fu, Janashrit Shrestha, Ayidh Almansour, Hong Wang, Anamika Gupta, Rohana Liyanage, Xiaolun Sun Mar 2025

The Mechanistic Target Of Rapamycin Mediates Clostridium Perfringens-Induced Chicken Necrotic Enteritis Attenuated By Secondary Bile Acid Deoxycholic Acid, Mohit Bansal, Tahrir Alenezi, Ying Fu, Janashrit Shrestha, Ayidh Almansour, Hong Wang, Anamika Gupta, Rohana Liyanage, Xiaolun Sun

Poultry Science Faculty Publications and Presentations

Clostridium perfringens is a prevalent gut bacterial pathogen in humans and animals. This study investigated the role of the mechanistic targets of rapamycin (mTOR) and deoxycholic acid (DCA) on C. perfringens intestinal infection. Chickens were sequentially infected with Eimeria maxima and received the mTOR inhibitor rapamycin and DCA. C. perfringens-induced necrotic enteritis (NE) was evaluated using body weight gain (BWG), histopathology, bile acids, pathogen colonization, cell infiltration and death, and gene expression. The significant difference of p < 0.05 was analyzed by one-way ANOVA and multiple comparisons. Notably, rapamycin strongly reduced the subclinical and clinical NE histopathologies. DCA and DCA combined with rapamycin alleviated clinical NE and BWG loss. Rapamycin, DCA, and DCA + rapamycin attenuated bile acid reduction in NE birds, and they also reduced immune cell infiltration into the intestinal lamina propria as well as immune cell migration in vitro. At molecular levels, DCA and DCA + rapamycin reduced proinflammatory IFN gamma, MMP9, IL23, and IL17 gene expression. Rapamycin, DCA, and DCA + rapamycin reduced NE-induced intestinal cell apoptosis. Together, these results suggest that mTOR signaling mediates C. perfringens-induced ileitis, and combining mTOR inhibition and DCA improves the intervention efficacy against NE ileitis and BWG loss.


Diverse Roles Of Stress-Responsive Rnp Granules In Oogenesis And Infertility, M. Rebecca Glineburg, Carolee Nguyen Mar 2025

Diverse Roles Of Stress-Responsive Rnp Granules In Oogenesis And Infertility, M. Rebecca Glineburg, Carolee Nguyen

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Effectively responding to cellular stress (e.g., nutrient deprivation, oxidative stress) is essential for cell and organismal survival. A protective mechanism is especially critical in developing oocytes, where a prolonged quiescent state and the inability to divide render oocytes highly susceptible to accumulating stress that can result in cell death if unaddressed. Despite the common view that stress granules are the primary stress-responsive ribonucleoprotein granule, accumulating evidence shows that in ovaries, other ribonucleoprotein granules also uniquely mediate gene regulation in response to stress. Here, we review recent insights into ribonucleoprotein granule dynamics and ribonucleoprotein granule protein function during stress in the …


From Genes To Patterns: A Framework For Modeling The Emergence Of Embryonic Development From Transcriptional Regulation, Jimena Garcia-Guillen, Ezzat El-Sherif Mar 2025

From Genes To Patterns: A Framework For Modeling The Emergence Of Embryonic Development From Transcriptional Regulation, Jimena Garcia-Guillen, Ezzat El-Sherif

School of Integrative Biological & Chemical Sciences Faculty Publications

Understanding embryonic patterning, the process by which groups of cells are partitioned into distinct identities defined by gene expression, is a central challenge in developmental biology. This complex phenomenon is driven by precise spatial and temporal regulation of gene expression across many cells, resulting in the emergence of highly organized tissue structures. While similar emergent behavior is well understood in other fields, such as statistical mechanics, the regulation of gene expression in development remains less clear, particularly regarding how molecular-level gene interactions lead to the large-scale patterns observed in embryos. In this study, we present a modeling framework that bridges …


The Present And Future Of Robotic Surgery In Breast Cancer And Breast Reconstruction, Brett Allen, Alexis Knutson, Noama Iftekhar, Casey Giles, Jarrell Patterson, Joshua Macdavid, Richard Baynosa Mar 2025

The Present And Future Of Robotic Surgery In Breast Cancer And Breast Reconstruction, Brett Allen, Alexis Knutson, Noama Iftekhar, Casey Giles, Jarrell Patterson, Joshua Macdavid, Richard Baynosa

Department of Plastic Surgery Faculty Research

Background: Breast cancer is the second most common cancer in women with an improving mortality rate and a growing need for reconstruction following oncologic resection. Advancements in robotic surgery and minimally invasive techniques have offered refinement to traditional open techniques of flap harvest for reconstruction, particularly regarding improved donor site morbidity. Methods: The literature review was based on a PubMed database search using the keyword “Robotic breast reconstruction” in conjunction with the Boolean operators “Flap”, “Latissimus”, and “DIEP” to specify the search. In total, 106 results were generated, which were then manually reviewed and condensed for a comprehensive stance on …


Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov Mar 2025

Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, …