Catherine Freudenreich

Last updated
Catherine H. Freudenreich
Alma mater Rice University (BA) Duke University (PhD)
Scientific career
FieldsMolecular biology
Institutions Tufts University
Doctoral advisor Kenneth Kreuzer
Other academic advisors Virginia Zakian (postdoctoral)
Website https://as.tufts.edu/biology/freudenreich-lab

Catherine Freudenreich is an American molecular biologist at Tufts University. Since 2019, Freudenreich has served as chair of the Department of Biology. [1]

Contents

Life and career

Freudenreich spent her childhood in Los Alamos, New Mexico, before attending Rice University, where she graduated in 1988 with a B.A in biology. [2] She received her PhD in 1994 from Duke University, where she studied inhibitor binding sites of Type II topoisomerases in the lab of Kenneth Kreuzer, and continued to do so as a postdoctoral researcher in the same lab. [3] Freudenreich then undertook further postdoctoral research at Princeton University with Virginia Zakian, studying CTG repeats in yeast. [4] [1]

After her postdoctoral studies, Freudenreich was appointed to an assistant professor position in the Department of Biology at Tufts University in 1999, where she is currently professor and department chair. [1]

Research

Freudenreich’s lab studies genome instability in yeast, with the aim of uncovering mechanisms of genetic disease and cancer. In particular, much of her research has focused on conserved trinucleotide repeat sequences, specifically CAG/CTG, and their contributions to genome fragility and instability. [5] [6] [7] Recently, Freudenreich’s group looked at CAG/CTG repeats in Huntington’s disease, finding that the cells’ attempts to repair CAG sequences often lead to large, deleterious deletions. [8] [9] [10]

Freudenreich has also notably studied how DNA repeat sequences contribute to DNA structures that can cause DNA breaks, and how the cell protects against genomic damage from these mechanisms. [5] [11] [12] [13]

Notable publications

  1. Freudenreich, Catherine H.; Kantrow, Sara M.; Zakian, Virginia A. (1998-02-06). "Expansion and Length-Dependent Fragility of CTG Repeats in Yeast". Science. 279 (5352): 853–856. doi:10.1126/science.279.5352.853. ISSN  0036-8075. [4]
  2. Lahiri, Mayurika; Gustafson, Tanya L; Majors, Elizabeth R; Freudenreich, Catherine H (2004-07-23). "Expanded CAG Repeats Activate the DNA Damage Checkpoint Pathway". Molecular Cell. 15 (2): 287–293. doi:10.1016/j.molcel.2004.06.034. ISSN  1097-2765. [6]
  3. Polleys, Erica J.; Del Priore, Isabella; Haber, James E.; Freudenreich, Catherine H. (2023-04-29). "Structure-forming CAG/CTG repeats interfere with gap repair to cause repeat expansions and chromosome breaks". Nature Communications. 14 (1): 2469. doi:10.1038/s41467-023-37901-2. ISSN  2041-1723. [9]
  4. Zhang, Haihua; Freudenreich, Catherine H. (2007-08). "An AT-Rich Sequence in Human Common Fragile Site FRA16D Causes Fork Stalling and Chromosome Breakage in S. cerevisiae". Molecular Cell. 27 (3): 367–379. doi:10.1016/j.molcel.2007.06.012. ISSN  1097-2765. PMC  2144737. PMID  17679088. [12]
  5. Kerrest, Alix; Anand, Ranjith P.; Sundararajan, Rangapriya; Bermejo, Rodrigo; Liberi, Giordano; Dujon, Bernard; Freudenreich, Catherine H.; Richard, Guy-Franck (2009-01-11). "SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination". Nature Structural & Molecular Biology. 16 (2): 159–167. doi:10.1038/nsmb.1544. ISSN  1545-9985. [14]
  6. House, Nealia C.M.; Yang, Jiahui H.; Walsh, Stephen C.; Moy, Jonathan M.; Freudenreich, Catherine H. (2014-09-18). "NuA4 Initiates Dynamic Histone H4 Acetylation to Promote High-Fidelity Sister Chromatid Recombination at Postreplication Gaps". Molecular Cell. 55 (6): 818–828. doi:10.1016/j.molcel.2014.07.007. ISSN  1097-2765. PMC  4169719. PMID  25132173. [15]
  7. Su, Xiaofeng A.; Freudenreich, Catherine H. (2017-10-03). "Cytosine deamination and base excision repair cause R-loop–induced CAG repeat fragility and instability in Saccharomyces cerevisiae". Proceedings of the National Academy of Sciences. 114 (40). doi:10.1073/pnas.1711283114. ISSN  0027-8424. PMC  5635916. PMID  28923949. [16]

Awards and honors

Related Research Articles

Repeated sequences are short or long patterns that occur in multiple copies throughout the genome. In many organisms, a significant fraction of the genomic DNA is repetitive, with over two-thirds of the sequence consisting of repetitive elements in humans. Some of these repeated sequences are necessary for maintaining important genome structures such as telomeres or centromeres.

<span class="mw-page-title-main">Origin of replication</span> Sequence in a genome

The origin of replication is a particular sequence in a genome at which replication is initiated. Propagation of the genetic material between generations requires timely and accurate duplication of DNA by semiconservative replication prior to cell division to ensure each daughter cell receives the full complement of chromosomes. This can either involve the replication of DNA in living organisms such as prokaryotes and eukaryotes, or that of DNA or RNA in viruses, such as double-stranded RNA viruses. Synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, organisms have evolved surprisingly divergent strategies that control replication onset. Although the specific replication origin organization structure and recognition varies from species to species, some common characteristics are shared.

In genetics, trinucleotide repeat disorders, a subset of microsatellite expansion diseases, are a set of over 30 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides increase in copy numbers until they cross a threshold above which they cause developmental, neurological or neuromuscular disorders. In addition to the expansions of these trinucleotide repeats, expansions of one tetranucleotide (CCTG), five pentanucleotide, three hexanucleotide, and one dodecanucleotide (CCCCGCCCCGCG) repeat cause 13 other diseases. Depending on its location, the unstable trinucleotide repeat may cause defects in a protein encoded by a gene; change the regulation of gene expression; produce a toxic RNA, or lead to production of a toxic protein. In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes.

<span class="mw-page-title-main">Chromosomal fragile site</span> Cytogenetic feature

A chromosomal fragile site is a specific heritable point on a chromosome that tends to form a gap or constriction and may tend to break when the cell is exposed to partial replication stress. Based on their frequency, fragile sites are classified as "common" or "rare". To date, more than 120 fragile sites have been identified in the human genome.

Recombination hotspots are regions in a genome that exhibit elevated rates of recombination relative to a neutral expectation. The recombination rate within hotspots can be hundreds of times that of the surrounding region. Recombination hotspots result from higher DNA break formation in these regions, and apply to both mitotic and meiotic cells. This appellation can refer to recombination events resulting from the uneven distribution of programmed meiotic double-strand breaks.

<span class="mw-page-title-main">Cohesin</span> Protein complex that regulates the separation of sister chromatids during cell division

Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.

A trinucleotide repeat expansion, also known as a triplet repeat expansion, is the DNA mutation responsible for causing any type of disorder categorized as a trinucleotide repeat disorder. These are labelled in dynamical genetics as dynamic mutations. Triplet expansion is caused by slippage during DNA replication, also known as "copy choice" DNA replication. Due to the repetitive nature of the DNA sequence in these regions, 'loop out' structures may form during DNA replication while maintaining complementary base pairing between the parent strand and daughter strand being synthesized. If the loop out structure is formed from the sequence on the daughter strand this will result in an increase in the number of repeats. However, if the loop out structure is formed on the parent strand, a decrease in the number of repeats occurs. It appears that expansion of these repeats is more common than reduction. Generally, the larger the expansion the more likely they are to cause disease or increase the severity of disease. Other proposed mechanisms for expansion and reduction involve the interaction of RNA and DNA molecules.

<span class="mw-page-title-main">RAD54L</span> Protein-coding gene in the species Homo sapiens

DNA repair and recombination protein RAD54-like is a protein that in humans is encoded by the RAD54L gene.

<span class="mw-page-title-main">MED15</span> Protein-coding gene in the species Homo sapiens

Mediator of RNA polymerase II transcription subunit 15, also known as Gal11, Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the MED15 gene.

SAE2 is a gene in budding yeast, coding for the protein Sae2, which is involved in DNA repair. Sae2 is a part of the homologous recombination process in response to double-strand breaks. It is best characterized in the yeast model organism Saccharomyces cerevisiae. Homologous genes in other organisms include Ctp1 in fission yeast, Com1 in plants, and CtIP in higher eukaryotes including humans.

<span class="mw-page-title-main">SMC6</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the SMC6 gene.

<span class="mw-page-title-main">JPH3</span> Protein-coding gene in the species Homo sapiens

Junctophilin-3 (JPH3) is a protein residing in humans that is encoded by the JPH3 gene. The gene is approximately 97 kilobases long and is located at chromosomal position 16q24.2. Junctophilin proteins are associated with the formation of junctional membrane complexes, which link the plasma membrane with the endoplasmic reticulum in excitable cells. JPH3 is localized to the brain and is associated with motor coordination and memory neurons.

<span class="mw-page-title-main">SMC5</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 5 is a protein encoded by the SMC5 gene in human.

Virginia Zakian is the Harry C. Wiess Professor in the Life Sciences in the Department of Molecular Biology at Princeton University. She is the director of the Zakian Lab, which has done important research in topics such as telomere-binding protein, telomere recombination, and telomere position effects, at Princeton University. She is a fellow at the American Academy of Microbiology and the American Association for the Advancement of Science., and is an elected member of the National Academy of Sciences (2018). Zakian served as the chair of "Princeton's Task force on the Status of Women Faculty in the Natural Sciences and Engineering at Princeton" from 2001-2003, in 2003 Zakian became Princeton University's representative to Nine Universities, Gender Equity Analysis She was elected as a member of the American Academy of Arts and Sciences in 2019.

<span class="mw-page-title-main">Sergei Mirkin</span> Russian-American molecular biologist

Sergei Mirkin is a Russian-American biologist who studies genome instability mediated by repetitive DNA during DNA replication and transcription. He is a professor of Genetics and Molecular Biology and holds the White Family Chair in Biology at Tufts University.

Whi2 or Whiskey 2 is a 55 kDa globular, scaffold protein located to cell periphery in Saccharomyces cerevisiae, which plays an essential role in regulating stress response pathways, apparently by passing input signals about nutrient availability on to stress responsive elements and autophagy/mitophagy mechanisms. It is encoded by a 1.46 kbp gene located on chromosome 15. Whi2p shares a conserved BTB structure domain to the family of human potassium channel tetramerization domain proteins (KCTDs). KCTD family members have been associated with several type of cancers and epilepsy disorders.

Repeat Associated Non-AUG translation, or RAN translation, is an irregular mode of mRNA translation that can occur in eukaryotic cells.

Jeannie T. Lee is a Professor of Genetics at Harvard Medical School and the Massachusetts General Hospital, and a Howard Hughes Medical Institute Investigator. She is known for her work on X-chromosome inactivation and for discovering the functions of a new class of epigenetic regulators known as long noncoding RNAs (lncRNAs), including Xist and Tsix.

<span class="mw-page-title-main">RRM3</span>

RRM3 is a gene that encodes a 5′-to-3′ DNA helicase known affect multiple cellular replication and repair processes and is most commonly studied in Saccharomyces cerevisiae. RRM3 formally stands for Ribosomal DNArecombination mutation 3. The gene codes for nuclear protein Rrm3p, which is 723 amino acids in length, and is part of a Pif1p DNA helicase sub-family that is conserved from yeasts to humans. RRM3 and its encoded protein have been shown to be vital for cellular replication, specifically associating with replication forks genome-wide. RRM3 is located on chromosome 8 in yeast cells and codes for 723 amino acids producing a protein that weighs 81,581 Da.

Unstable DNA sequence are segments of genetic material that exhibit high rates of mutation or variation over time, resulting in significant genetic diversity within populations or even individual organisms.

References

  1. 1 2 3 "Catherine Freudenreich Faculty Profile". facultyprofiles.tufts.edu. Retrieved 2024-06-18.
  2. ↑ "Catherine H. Freudenreich | Brief bio". Frontiers Loop.
  3. ↑ Freudenreich, C H; Kreuzer, K N (1994-11-08). "Localization of an aminoacridine antitumor agent in a type II topoisomerase-DNA complex". Proceedings of the National Academy of Sciences. 91 (23): 11007–11011. Bibcode:1994PNAS...9111007F. doi: 10.1073/pnas.91.23.11007 . ISSN   0027-8424. PMC   45155 . PMID   7971998.
  4. 1 2 Freudenreich, Catherine H.; Kantrow, Sara M.; Zakian, Virginia A. (1998-02-06). "Expansion and Length-Dependent Fragility of CTG Repeats in Yeast". Science. 279 (5352): 853–856. Bibcode:1998Sci...279..853F. doi:10.1126/science.279.5352.853. ISSN   0036-8075. PMID   9452383.
  5. 1 2 "Research Overview | Department of Biology". as.tufts.edu. Retrieved 2024-06-18.
  6. 1 2 Lahiri, Mayurika; Gustafson, Tanya L; Majors, Elizabeth R; Freudenreich, Catherine H (2004-07-23). "Expanded CAG Repeats Activate the DNA Damage Checkpoint Pathway". Molecular Cell. 15 (2): 287–293. doi:10.1016/j.molcel.2004.06.034. ISSN   1097-2765. PMID   15260979.
  7. ↑ Howard, Marjorie. "New fellowship offers undergraduate research opportunities". web.mit.edu. Retrieved 2024-07-12.
  8. ↑ "How DNA Repair Can Go Wrong and Lead to Disease | Tufts Now". now.tufts.edu. 2023-05-10. Retrieved 2024-06-18.
  9. 1 2 Polleys, Erica J.; Del Priore, Isabella; Haber, James E.; Freudenreich, Catherine H. (2023-04-29). "Structure-forming CAG/CTG repeats interfere with gap repair to cause repeat expansions and chromosome breaks". Nature Communications. 14 (1): 2469. Bibcode:2023NatCo..14.2469P. doi:10.1038/s41467-023-37901-2. ISSN   2041-1723. PMC   10148874 . PMID   37120647.
  10. ↑ "Understanding the Link Between DNA Mutations & Repair Dysfunction | Genetics And Genomics". Labroots. Retrieved 2024-06-24.
  11. ↑ Pennisi, Elizabeth (2006-06-09). "DNA's Molecular Gymnastics". Science. 312 (5779): 1467–1468. doi:10.1126/science.312.5779.1467. ISSN   0036-8075. PMID   16763129.
  12. 1 2 Zhang, Haihua; Freudenreich, Catherine H. (2007-08-03). "An AT-Rich Sequence in Human Common Fragile Site FRA16D Causes Fork Stalling and Chromosome Breakage in S. cerevisiae". Molecular Cell. 27 (3): 367–379. doi:10.1016/j.molcel.2007.06.012. ISSN   1097-2765. PMC   2144737 . PMID   17679088.
  13. ↑ "Mapping the Kinks in Faulty DNA | Tufts Now". now.tufts.edu. 2019-08-01. Retrieved 2024-06-18.
  14. ↑ Kerrest, Alix; Anand, Ranjith P.; Sundararajan, Rangapriya; Bermejo, Rodrigo; Liberi, Giordano; Dujon, Bernard; Freudenreich, Catherine H.; Richard, Guy-Franck (2009-01-11). "SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination". Nature Structural & Molecular Biology. 16 (2): 159–167. doi:10.1038/nsmb.1544. ISSN   1545-9985. PMC   4454460 . PMID   19136956.
  15. ↑ House, Nealia C.M.; Yang, Jiahui H.; Walsh, Stephen C.; Moy, Jonathan M.; Freudenreich, Catherine H. (2014-09-18). "NuA4 Initiates Dynamic Histone H4 Acetylation to Promote High-Fidelity Sister Chromatid Recombination at Postreplication Gaps". Molecular Cell. 55 (6): 818–828. doi:10.1016/j.molcel.2014.07.007. ISSN   1097-2765. PMC   4169719 . PMID   25132173.
  16. ↑ Su, Xiaofeng A.; Freudenreich, Catherine H. (2017-10-03). "Cytosine deamination and base excision repair cause R-loop–induced CAG repeat fragility and instability in Saccharomyces cerevisiae". Proceedings of the National Academy of Sciences. 114 (40): E8392–E8401. Bibcode:2017PNAS..114E8392S. doi: 10.1073/pnas.1711283114 . ISSN   0027-8424. PMC   5635916 . PMID   28923949.
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