Abby Dernburg

Last updated
Abby Dernburg
Alma mater University of California, Berkeley, BA
University of California, San Francisco, PhD
Spouse Gary Karpen
Scientific career
Fields Cell biology, Genetics
Institutions University of California, Berkeley
Lawrence Berkeley National Laboratory
Howard Hughes Medical Institute
Academic advisors Clayton Heathcock
Dan Koshland
John Sedat
Anne Villeneuve
Website Research website

Abby F. Dernburg is a professor of Cell and Developmental Biology at the University of California, Berkeley, an Investigator of the Howard Hughes Medical Institute, and a Faculty Senior Scientist at Lawrence Berkeley National Laboratory.

Contents

Education and early career

Dernburg received her Bachelor of Arts in Biochemistry in 1987 from the University of California, Berkeley. There, she spent half a year working in an organic chemistry lab before she joined Dan Koshland's laboratory, studying bacterial chemotaxis, or how cells and organisms move in response to a chemical stimulus. [1] Following graduation, she spent a year working as a research technician in Koshland's lab, where she co-authored a study analyzing the structure of a bacterial sensory receptor. [2]

Dernburg then entered the Tetrad Program at the University of California, San Francisco for her doctoral work. She received her PhD in 1996 working in the laboratory of John Sedat studying several aspects of chromosomes organization and function. She developed fluorescence in situ hybridization (FISH) methods to study the genetic content of cells and to investigate how chromosomes are organized within cell nuclei. Using these tools she investigated how chromosome organization within the nucleus can affect transcription, and how chromosomes interact to separate from each during the process of meiosis, using the fly Drosophila as a model organism. [3] [4] Specifically, she used FISH to monitor the chromosomal position of regions of heterochromatin—a tightly packed region of DNA associated with non-expressed genes—and of a fly gene called brown, which codes for the red pigment that gives the flies their red eyes; when the brown gene is turned off, flies have brown eyes. Heterochromatic regions of chromosomes tend to associate together in a specific compartment of the nucleus. Dernburg found that when a region of heterochromatin was inserted near the brown gene, the gene would associate with a heterochromatic region of the nucleus and would thus be inactivated, giving flies with this insertion brown eyes. The study demonstrated the effect of chromosomal positioning on gene expression. Dernburg also studied the role heterochromatin plays in chromosome segregation during meiosis, finding that the heterochromatic regions of homologous chromosomes remain associated with one another until metaphase I, or the stage at which chromosomes line up along the center of the nucleus prior to the first round of meiotic division. [5] This association ensures that the resulting daughter cells have the appropriate number of chromosomes. She completed her dissertation, called Nuclear Architecture in Drosophila melanogaster, documenting this work in 1996. [6] Her thesis received the Larry Sandler Memorial Award in 1997 from the Genetics Society of America, which recognizes the most outstanding dissertation in the area of Drosophila genetics and biology. [7]

For her postdoctoral research, Dernburg joined the laboratory of Anne Villeneuve at Stanford University, where she transitioned to working on the nematode worm Caenorhabditis elegans . [1] There, focused on the process of meiosis, which she continues to study in her own lab, she adapted FISH methods to study the cytology of chromosome pairing in the worm. [7] In 1998, she published a study documenting how meiosis in the worm is distinct from meiosis in many other eukaryotic organisms. In most eukaryotes, double-strand breaks in the DNA are required for pairing and synapsis between homologous chromosomes during meiosis. Dernburg found that in Caenorhabditis elegans, double-strand breaks are required for recombination and for chromosome segregation during meiosis, but not for homologous pairing and synapsis. [8] The finding suggested that there may be more diversity in meiotic mechanisms than was previously expected. [7]

Research

In 2000, Dernburg started up her laboratory at Lawrence Berkeley National Laboratory and the University of California, Berkeley to continue investigating chromosome organization and dynamics, focusing on meiosis using the nematode worm Caenorhabditis elegans as a model organism. [9] Her laboratory has contributed to the community's understanding of how chromosomes find and pair with the appropriate homolog during meiosis, which is essential for proper chromosome segregation and ensuring the appropriate chromosome copy number in daughter cells. Her group has worked to understand how special regions of chromosomes, known as pairing centers, promote homologous chromosome pairing, synapsis, and segregation in the worm. In 2005, they published a study demonstrating how pairing centers perform two separable functions during meiosis. [10] [11] First, they facilitate pairing through stabilizing an intermediate complex involved in the pairing process. Second, pairing centers promote the formation of a synaptonemal complex, in which a protein polymer acts as a scaffold to hold homologous chromosomes together during recombination. In a related study, her group also uncovered a conserved meiotic checkpoint that acts during meiosis to recognize unpaired/unsynapsed chromosomes. [11] [12] Cells identified as having unsynapsed chromosomes undergo apoptosis, or programmed cell death, to guard against the formation of sex cells with the wrong number of chromosomes. [12]

Dernburg's group also discovered that the functions of pairing centers depend on a family of four DNA-binding zinc-finger proteins—called HIM or ZIM proteins—that recognize and bind short, repetitive sequences that are hallmarks of pairing centers. [13] Each him or zim protein recognizes a particular pairing center sequence to help bring homologous chromosomes together. [13] [14] Dernburg's group first uncovered the him-8 gene, which encodes a protein responsible for proper meiotic separation of the worm's X chromosome. [15] These proteins facilitate an interaction between the pairing centers and a complex of microtubules and a motor protein called dynein, which allow chromosomes to move along the nuclear envelope until they encounter their partner. [1]

Dernburg has also moved beyond the nematode worm to begin to study meiotic mechanisms in planarians, which are non-parasitic flatworms, as well as another species of nematode called Pristionchus pacificus to understand how meiotic mechanisms are conserved—or diverge—across species. [1]

The Dernburg lab also develops methods for microscopy of living nematodes. Using live cell imaging they discovered that the synaptonemal complex, the special structure that holds together homologous chromosomes and enables them to undergo meiotic recombination, is a liquid crystal. [16] This has led them to propose a mechanism for crossover interference based on a reaction–diffusion mechanism. [17]

In 2008, Dernburg became a Howard Hughes Medical Institute Investigator. [18] She also has a joint appointment as a Faculty Senior Scientist at Lawrence Berkeley National Laboratory.

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a zygote, a cell with two copies of each chromosome again.

<span class="mw-page-title-main">Chromosomal crossover</span> Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

<span class="mw-page-title-main">Prophase</span> First phase of cell division in both mitosis and meiosis

Prophase is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus.

<span class="mw-page-title-main">Homologous chromosome</span> Chromosomes that pair in fertilization

A pair of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci, where they provide points along each chromosome that enable a pair of chromosomes to align correctly with each other before separating during meiosis. This is the basis for Mendelian inheritance, which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area.

<span class="mw-page-title-main">Synaptonemal complex</span> Protein structure

The synaptonemal complex (SC) is a protein structure that forms between homologous chromosomes during meiosis and is thought to mediate synapsis and recombination during prophase I during meiosis in eukaryotes. It is currently thought that the SC functions primarily as a scaffold to allow interacting chromatids to complete their crossover activities.

<span class="mw-page-title-main">Synapsis</span> Biological phenomenon in meiosis

Synapsis or Syzygy is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis. When homologous chromosomes synapse, their ends are first attached to the nuclear envelope. These end-membrane complexes then migrate, assisted by the extranuclear cytoskeleton, until matching ends have been paired. Then the intervening regions of the chromosome are brought together, and may be connected by a protein-DNA complex called the synaptonemal complex. During synapsis, autosomes are held together by the synaptonemal complex along their whole length, whereas for sex chromosomes, this only takes place at one end of each chromosome.

Zygotene is the second stage of prophase I during meiosis, the specialized cell division that reduces the chromosome number by half to produce haploid gametes. It follows the leptotene stage.

The pachytene stage, also known as pachynema, is the third stage of prophase I during meiosis, the specialized cell division that reduces chromosome number by half to produce haploid gametes. It follows the zygotene stage.

<span class="mw-page-title-main">Bivalent (genetics)</span>

A bivalent is one pair of chromosomes in a tetrad. A tetrad is the association of a pair of homologous chromosomes physically held together by at least one DNA crossover. This physical attachment allows for alignment and segregation of the homologous chromosomes in the first meiotic division. In most organisms, each replicated chromosome elicits formation of DNA double-strand breaks during the leptotene phase. These breaks are repaired by homologous recombination, that uses the homologous chromosome as a template for repair. The search for the homologous target, helped by numerous proteins collectively referred as the synaptonemal complex, cause the two homologs to pair, between the leptotene and the pachytene phases of meiosis I.

<span class="mw-page-title-main">Spo11</span> Protein-coding gene in the species Homo sapiens

Spo11 is a protein that in humans is encoded by the SPO11 gene. Spo11, in a complex with mTopVIB, creates double strand breaks to initiate meiotic recombination. Its active site contains a tyrosine which ligates and dissociates with DNA to promote break formation. One Spo11 protein is involved per strand of DNA, thus two Spo11 proteins are involved in each double stranded break event.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

<span class="mw-page-title-main">MSH5</span> Protein-coding gene in the species Homo sapiens

MutS protein homolog 5 is a protein that in humans is encoded by the MSH5 gene.

<span class="mw-page-title-main">DMC1 (gene)</span> Protein-coding gene in the species Homo sapiens

Meiotic recombination protein DMC1/LIM15 homolog is a protein that in humans is encoded by the DMC1 gene.

<span class="mw-page-title-main">MSH4</span> Protein-coding gene in the species Homo sapiens

MutS protein homolog 4 is a protein that in humans is encoded by the MSH4 gene.

<span class="mw-page-title-main">Meiotic recombination checkpoint</span>

The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed.

The leptotene stage, also known as leptonema, is the first of five substages of prophase I during meiosis, the specialized cell division that reduces the chromosome number by half to produce haploid gametes in sexually reproducing organisms.

<span class="mw-page-title-main">Synthesis-dependent strand annealing</span>

Synthesis-dependent strand annealing (SDSA) is a major mechanism of homology-directed repair of DNA double-strand breaks (DSBs). Although many of the features of SDSA were first suggested in 1976, the double-Holliday junction model proposed in 1983 was favored by many researchers. In 1994, studies of double-strand gap repair in Drosophila were found to be incompatible with the double-Holliday junction model, leading researchers to propose a model they called synthesis-dependent strand annealing. Subsequent studies of meiotic recombination in S. cerevisiae found that non-crossover products appear earlier than double-Holliday junctions or crossover products, challenging the previous notion that both crossover and non-crossover products are produced by double-Holliday junctions and leading the authors to propose that non-crossover products are generated through SDSA.

Holocentric chromosomes are chromosomes that possess multiple kinetochores along their length rather than the single centromere typical of other chromosomes. They were first described in cytogenetic experiments in 1935. Since this first observation, the term holocentric chromosome has referred to chromosomes that: i) lack the primary constriction corresponding to the centromere observed in monocentric chromosomes; and ii) possess multiple kinetochores dispersed along the entire chromosomal axis, such that microtubules bind to the chromosome along its entire length and move broadside to the pole from the metaphase plate. Holocentric chromosomes are also termed holokinetic, because, during cell division, the sister chromatids move apart in parallel and do not form the classical V-shaped figures typical of monocentric chromosomes.

Glenna Shirleen Roeder is a geneticist known for identifying and characterizing the yeast genes that regulate the process of meiosis with particular emphasis on synapsis.

<span class="mw-page-title-main">Anne Villeneuve (scientist)</span> American geneticist

Anne Villeneuve is an American geneticist. She is known for her work on the mechanisms governing chromosome inheritance during sexual reproduction. Her work focuses on meiosis, the process by which a diploid organism, having two sets of chromosomes, produces gametes with only one set of chromosomes. She is a Professor of Developmental Biology and of Genetics at Stanford University and a member of the National Academy of Sciences.

References

  1. 1 2 3 4 "Meiosis Maven". The Scientist Magazine®. Retrieved 2018-12-31.
  2. ↑ Falke, J; Dernburg, AF; Sternberg, DA; Zalkin, N; Milligan, DL; Koshland, DE (1988-11-01). "Structure of a bacterial sensory receptor. A site-directed sulfhydryl study". The Journal of Biological Chemistry. 263 (29): 14850–8. doi: 10.1016/S0021-9258(18)68117-7 . PMID   3049592.
  3. ↑ Dernburg, Abby F.; Broman, Karl W.; Fung, Jennifer C.; Marshall, Wallace F.; Philips, Jennifer; Agard, David A.; Sedat, John W. (1996-05-31). "Perturbation of Nuclear Architecture by Long-Distance Chromosome Interactions". Cell. 85 (5): 745–759. doi: 10.1016/S0092-8674(00)81240-4 . ISSN   0092-8674. PMID   8646782.
  4. ↑ Wells, William. "Don't write off 'junk' DNA". New Scientist. Retrieved 2019-01-01.
  5. ↑ Dernburg, Abby F.; Sedat, John W.; Hawley, R. Scott (1996-07-12). "Direct Evidence of a Role for Heterochromatin in Meiotic Chromosome Segregation". Cell. 86 (1): 135–146. doi: 10.1016/S0092-8674(00)80084-7 . ISSN   0092-8674. PMID   8689681.
  6. ↑ "Nuclear architecture in drosophila melanogaster /". ResearchGate. Retrieved 2019-01-08.
  7. 1 2 3 4 Hawley, R. Scott (April 2011). "The 2011 Novitski Prize: Abby F. Dernburg". Genetics. 187 (4): 999–1000. doi:10.1534/genetics.111.127829. ISSN   0016-6731. PMC   3070538 .
  8. ↑ Dernburg, Abby F.; McDonald, Kent; Moulder, Gary; Barstead, Robert; Dresser, Michael; Villeneuve, Anne M. (1998-08-07). "Meiotic Recombination in C. elegans Initiates by a Conserved Mechanism and Is Dispensable for Homologous Chromosome Synapsis". Cell. 94 (3): 387–398. doi: 10.1016/S0092-8674(00)81481-6 . ISSN   0092-8674. PMID   9708740.
  9. ↑ "Dernburg Lab". mcb.berkeley.edu. Retrieved 2019-01-08.
  10. ↑ MacQueen, Amy J.; Phillips, Carolyn M.; Bhalla, Needhi; Weiser, Pinky; Villeneuve, Anne M.; Dernburg, Abby F. (2005-12-16). "Chromosome Sites Play Dual Roles to Establish Homologous Synapsis during Meiosis in C. elegans". Cell. 123 (6): 1037–1050. doi:10.1016/j.cell.2005.09.034. ISSN   0092-8674. PMC   4435800 . PMID   16360034.
  11. 1 2 "Research News: Learning About Sex From an Elegant Worm". www2.lbl.gov. Retrieved 2019-01-08.
  12. 1 2 Bhalla, Needhi; Dernburg, Abby F. (2005-12-09). "A conserved checkpoint monitors meiotic chromosome synapsis in Caenorhabditis elegans". Science. 310 (5754): 1683–1686. Bibcode:2005Sci...310.1683B. doi:10.1126/science.1117468. ISSN   1095-9203. PMID   16339446. S2CID   37038648.
  13. 1 2 Preuss, Paul (2006-12-04). "New Clues to How Sex Evolves | Berkeley Lab". News Center. Retrieved 2019-01-08.
  14. ↑ Phillips, Carolyn M.; Dernburg, Abby F. (December 2006). "A family of zinc-finger proteins is required for chromosome-specific pairing and synapsis during meiosis in C. elegans". Developmental Cell. 11 (6): 817–829. doi: 10.1016/j.devcel.2006.09.020 . ISSN   1534-5807. PMID   17141157.
  15. ↑ Phillips, Carolyn M.; Wong, Chihunt; Bhalla, Needhi; Carlton, Peter M.; Weiser, Pinky; Meneely, Philip M.; Dernburg, Abby F. (2005-12-16). "HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis". Cell. 123 (6): 1051–1063. doi:10.1016/j.cell.2005.09.035. ISSN   0092-8674. PMC   4435792 . PMID   16360035.
  16. ↑ Rog, Ofer; Köhler, Simone; Dernburg, Abby F. (2017). "The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors". eLife. 6. doi: 10.7554/eLife.21455 . PMC   5268736 . PMID   28045371.
  17. ↑ Zhang, Liangyu; Köhler, Simone; Rillo-Bohn, Regina; Dernburg, Abby F. (2018). "A compartmentalized signaling network mediates crossover control in meiosis". eLife. 7. doi: 10.7554/eLife.30789 . PMC   5906097 . PMID   29521627.
  18. ↑ "Abby F. Dernburg". HHMI.org. Retrieved 2019-01-01.
  19. ↑ "ARCHIVED - The Presidential Early Career Award for Scientists and Engineers (PECASE) Program Archive - OER Public Websites Archive Page". archives.nih.gov. Retrieved 2018-12-31.
  20. ↑ "Dernburg and Nogales Named Fellows of the American Society for Cell Biology". Biosciences Area. 2017-11-28. Retrieved 2018-12-31.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.