Virginia Zakian

Last updated
Virginia Zakian
Alma mater Cornell University
Yale University
Known for Molecular Biology
Telomeres
Chromosome Instability
AwardsFellow at the American Academy of Microbiology (1993-)
Fellow at the American Association for the Advancement of Science (1992-)
Member of the National Academy of Sciences (2018)
Scientific career
Fields Biology
Molecular Biology
Institutions Princeton University
University of Washington
Fred Hutchinson Cancer Research Center
Doctoral students Wai-Hong Tham

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. [1] She is a fellow at the American Academy of Microbiology and the American Association for the Advancement of Science., [2] 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 [2] [3] She was elected as a member of the American Academy of Arts and Sciences in 2019. [4]

Contents

Education and career

Zakian completed her A.B. in Biology at Cornell University, graduating cum laude and with distinction in all subjects, in 1970. [2] Zakian went on to pursue graduate work in Biology at Yale University, while she was working on her Ph.D. (1970–1973) she received a NSF predoctoral fellowship. [2] In 1975, Zakian completed her Ph.D. in Biology, her thesis was supervised by Joseph G. Gall and concerned "DNA replication in Drosophila." [2] Zakian served as a postdoctoral fellow at Princeton University from 1975–1976, during this time she conducted research on "animal virus replication" with Dr. AJ Levine. [2] Later in 1976, Zakian continued her postdoctoral research at the University of Washington where she worked on research concerning "yeast DNA Replication" with Dr. WL Fangman. [2]

In 1978, Zakian joined the Fred Hutchinson Cancer Research Center as an assistant member, Zakian was promoted to the position of an "associate member" in 1984 and to the position of"full member" in 1987. During her time at the Fred Hutchinson Cancer Research Center, Zakian published or co-published around sixty articles in peer-reviewed journals like Nature (journal), Cell (journal), Proceedings of the National Academy of Sciences of the United States of America and the Journal of Molecular Biology. [2] [5] Additionally, during her stay at Fred Hutchinson, Zakian served as either an editor, associate editor or member of the editorial board of journals such as: Plasmid (1986–90), Chromosoma (1990–), J. Exptl. Zoology (1991–96), Trends in Cell Biology (1991–97), Molecular and Cellular Biology (1992–98), Genes to Cells (1994–98). [2]

In 1995, Zakian was appointed as a professor in the Department of Molecular Biology at Princeton University. [2] Zakian was awarded the Harry C. Wiess Professor in the Life Sciences in the Department of Molecular Biology in the year 2000, a position that she holds to this day. [6] 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 [2] [3]

Research Area

Zakian has published 150 papers in peer-reviewed journals throughout her career. [5] Most of Zakian's research concerns telomeres, which are "the region[s] of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes." [3] Zakian's lab " uses a combination of genetic, biochemical, and cell biological approaches to identify proteins that affect telomeres and to determine their mechanism of action." [7] One of the lab's "major goal[s] is to understand how telomeres, the physical ends of chromosomes, contribute to chromosome stability." [7]

Zakian, along with GM Dani, "were the first to construct and characterize a linear artificial chromosome." in 1983. [1] This work, along with another related study [8] helped to introduce the "use ciliate telomeres to generate linear yeast episomes, a strategy that began the molecular era of yeast telomere biology" [1] Zakian, working with a team of other researchers in the paper "Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription" (Gottschling et al. 1990 Cell) [9] "discovered telomere position effect, TPE, the transcriptional repression of genes near telomeres in budding yeast." [1] In 1994, Zakian, along with Schulz, "identified the Pif1p DNA helicase as an inhibitor of telomere lengthening and especially of telomere formation." [7] In "Pif1p helicase, a catalytic inhibitor of telomerase in yeast." [10] a team of researchers, including Zakian, found that "Pif1p-like helicases are found in diverse organisms, including humans" and that "Pif1p is the prototype member of a helicase subfamily" [1] The team proposed that "Pif1p-mediated inhibition of telomerase promotes genetic stability by suppressing telomerase-mediated healing of double-strand breaks." [10] Ivessa, Zhou and Zakian later discovered another, "highly connected," member of Pif1p's "helicase subfamily" called Rrm3p. [7] In their paper they found that both Pif1p and Rrm3p both "affected rDNA replication but had opposing effects on fork progression." On the one hand, "Pif1p helped maintain the replication fork progression" while "Rrm3p appears to be the replicative helicase for rDNA as it acted catalytically to promote fork progression throughout the rDNA." [11]

Selected publications

Related Research Articles

<span class="mw-page-title-main">Cell cycle</span> Series of events and stages that result in cell division

The cell cycle, or cell-division cycle, is the series of events that take place in a cell that causes it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.

<span class="mw-page-title-main">DNA replication</span> Biological process

In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part of biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential.

<span class="mw-page-title-main">Telomere</span> Region of repetitive nucleotide sequences on chromosomes

A telomere is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.

<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.

<span class="mw-page-title-main">Elizabeth Blackburn</span> Australian-born American biological researcher

Elizabeth Helen Blackburn, is an Australian-American Nobel laureate who is the former president of the Salk Institute for Biological Studies. In 1984, Blackburn co-discovered telomerase, the enzyme that replenishes the telomere, with Carol W. Greider. For this work, she was awarded the 2009 Nobel Prize in Physiology or Medicine, sharing it with Carol W. Greider and Jack W. Szostak, becoming the first Australian woman Nobel laureate.

Subtelomeres are segments of DNA between telomeric caps and chromatin.

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Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, and MDS/AML, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing and cognitive impairment can be a feature. The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.

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In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex that binds in all eukaryotes and archaea in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes. ORC is a central component for eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle.

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<span class="mw-page-title-main">Eukaryotic DNA replication</span> DNA replication in eukaryotic organisms

Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.

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

The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas.

<span class="mw-page-title-main">Telomerase RNA component</span> NcRNA found in eukaryotes

Telomerase RNA component, also known as TR, TER or TERC, is an ncRNA found in eukaryotes that is a component of telomerase, the enzyme used to extend telomeres. TERC serves as a template for telomere replication by telomerase. Telomerase RNAs differ greatly in sequence and structure between vertebrates, ciliates and yeasts, but they share a 5' pseudoknot structure close to the template sequence. The vertebrate telomerase RNAs have a 3' H/ACA snoRNA-like domain.

Shelterin is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang. Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement-loop).

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<span class="mw-page-title-main">Telomeric repeat–containing RNA</span> Long non-coding RNA transcribed from telomeres

Telomeric repeat–containing RNA (TERRA) is a long non-coding RNA transcribed from telomeres - repetitive nucleotide regions found on the ends of chromosomes that function to protect DNA from deterioration or fusion with neighboring chromosomes. TERRA has been shown to be ubiquitously expressed in almost all cell types containing linear chromosomes - including humans, mice, and yeasts. While the exact function of TERRA is still an active area of research, it is generally believed to play a role in regulating telomerase activity as well as maintaining the heterochromatic state at the ends of chromosomes. TERRA interaction with other associated telomeric proteins has also been shown to help regulate telomere integrity in a length-dependent manner.

<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.

<span class="mw-page-title-main">PIF1 5'-to-3' DNA helicase</span> Protein-coding gene in the species Homo sapiens

PIF1 5'-to-3' DNA helicase is a protein that in humans is encoded by the PIF1 gene.

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References

  1. 1 2 3 4 5 "Zakian Summary of Research Accomplishments". Zakian Lab. Archived from the original on 2010-06-19.
  2. 1 2 3 4 5 6 7 8 9 10 11 "Virginia A. Zakian Biographical Information". Zakian Lab. Archived from the original on 2006-09-01.
  3. 1 2 3 "Virginia Zakian". Princeton University. Archived from the original on 2007-11-22.
  4. ↑ "Virginia A. Zakian". American Academy of Arts & Sciences. Retrieved 2021-02-11.
  5. 1 2 "Zakian Publications". Zakian Lab. Archived from the original on 2006-09-03.
  6. ↑ "Endowed Professors and other chairs". Princeton University. Archived from the original on 2008-05-14.
  7. 1 2 3 4 "Virginia A. Zakian". Princeton. Retrieved 2013-10-14.
  8. ↑ Pluta, AF; Dani GM; Spear BB; Zakian VA (March 1984). "Elaboration of telomeres in yeast: Recognition and modification of termini from Oxytricha macronuclear DNA". PNAS. 81 (5): 1475–79. Bibcode:1984PNAS...81.1475P. doi: 10.1073/pnas.81.5.1475 . PMC   344859 . PMID   6324194.
  9. ↑ Zakian, Virginia; Daniel E. Gottschling; Oscar M. Aparicio; Barbara L. Billington (16 November 1990). "Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription". Cell. 63 (4): 751–762. doi:10.1016/0092-8674(90)90141-z. PMID   2225075. S2CID   21940834 . Retrieved 2013-10-14.
  10. 1 2 Zhou, J; Monson EK; Teng SC; Schulz VP; Zakian VA (September 2000). "Pif1p helicase, a catalytic inhibitor of telomerase in yeast". Science. 289 (5480): 771–4. Bibcode:2000Sci...289..771Z. doi:10.1126/science.289.5480.771. PMID   10926538.
  11. ↑ Ivessa, Andreas; Jin-Qiu Zhou; Virginia A Zakian (18 February 2000). "The Saccharomyces Pif1p DNA Helicase and the Highly Related Rrm3p Have Opposite Effects on Replication Fork Progression in Ribosomal DNA". Cell. 100 (4): 479–89. doi: 10.1016/S0092-8674(00)80683-2 . PMID   10693764.
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