- how chromosomes can find their homolog during meiosis,
- the structure and function of the giant protein structure that connects them known as the synaptonemal complex, and
- how paired homologs can segregate from their partners.
Chromosome synapsis, recombination, & segregation
We are highly focused on understanding the process of pairing, with an emphasis on understanding the roles of centromeres and heterochromatin in mediating this process. We are also intent on elucidating the structure and function of the SC and the various roles that it plays in meiosis. Although much is known about the structure and the composition of the SC, critical questions remain regarding its function and the detailed topology of its components.
Why we care so much about this problem: From a basic research perspective we want to understand meiosis because it is the physical basis of Mendel’s Laws. We also know that a knowledge of meiosis will answer the question of how two chromosomes pair. But, in a broader sense, we are aware that improper meiosis is a common cause of miscarriage, impaired fertility, and birth defects in human beings. We know, for example, that the risk of certain kinds of meiotic failures (the generation of trisomies) greatly increases with advancing maternal age. The ability to address these issues, and perhaps someday ameliorate them, will come only when we know what goes “wrong” to cause them – and that can come only when we fully understand how meiosis actually works.
Scott Hawley, Ph.D.
-Investigator and American Cancer Society Research Professor
-Dean Emeritus, The Graduate School of the Stowers Institute
-Professor of Molecular and Integrative Physiology School of Medicine, University of Kansas Medical Center
-Adjunct Professor, School of Biological Science, University of Missouri at Kansas City
I need to do both to live."
Fellow, American Association for the Advancement of Science
American Academy of Arts and Sciences
President, Genetics Society of America
National Academy of Sciences
Chair, NIH NICHD Developmental Biology Subcommittee
Excellence in Education Award - Genetics Society of America
George W. Beadle Award Genetics Society of America
American Cancer Society Excellence in Research Award
University of California, Riverside
University of Washington
Selected Research Papers
Regulation of Polo Kinase by Matrimony Is Required for Cohesin Maintenance during Drosophila melanogaster Female Meiosis
Curr Biol. 2020.
X chromosome and autosomal recombination are differentially sensitive to disruptions in SC maintenance
Billmyre KK, Cahoon CK, Heenan GM, Wesley ER, Yu Z, Unruh JR, Takeo S, Hawley RS. Proc Natl Acad Sci U S A. 2019;116:21641-21650.
The E3 ubiquitin ligase SINA regulates the assembly and disassembly of the synaptonemal complex in Drosophila females
Hughes SE, Hemenway E, Guo F, Yi K, Yu Z, Hawley RS. PLoS Genet. 2019;15:e1008161. doi: 10.1371/journal.pgen.1008161.
Narya, a RING finger domain-containing protein, is required for both meiotic DNA double-strand break formation and crossover maturation in Drosophila melanogaster
Lake CM, Nielsen RJ, Bonner AM, Eche S, White-Brown S, McKim KS, Hawley RS. PLoS Genet. 2019;15:e1007886. doi: 1007810.1001371/journal.pgen.1007886.
Reviews, Commentaries, Chapters or Books
Alternative Synaptonemal Complex Structures: Too Much of a Good Thing?
[published ahead of print August 13 2020]. Trends Genet. 2020.
Meiosis: Location, Location, Location, How Crossovers Ensure Segregation
Curr Biol. 2020
The Human Genome, A User's Guide.
Third ed: Academic Press; 2011.
Drosophila: A Laboratory Handbook
2nd ed. New York: Cold Spring Harbor Press, 2005. 1409 p.
Advanced Genetic Analysis: Finding Meaning in a Genome.
Boston: Blackwell Publishing, 2003. 256 p.
New York: Cold Spring Harbor Press, 2000. 724 p.
Undergraduate Researcher, Emily Wesley, earns first authorship in Chromosoma
Katie Billmyre receives a K99 award
Stacie Hughes publishes a review about Alternative Synaptonemal Complexes in Trends in Genetics’ November 2020Read more
Hughes SE, Hawley RS.[published ahead of print August 13 2020]. Trends Genet. 2020.
The synaptonemal complex (SC), a highly conserved structure built between homologous meiotic chromosomes, is required for crossover formation and ensuring proper chromosome segregation. In many organisms, SC components can also form alternative structures, including repeating SC structures that are known as polycomplexes (PCs), and extensively modified SC structures that are maintained late in meiosis. PCs display differences in their ability to localize with lateral element proteins, recombination machinery, and DNA. They can be created by defects in post-translational modification, suggesting that these modifications have roles in preventing alternate SC structures. These SC-like structures provide insight into the rules for building and maintaining the SC by offering an 'in vivo laboratory' for models of SC assembly, structure, and disassembly. Here, we discuss what these structures can tell us about the rules for building the SC and the roles of the SC in meiotic processes.
chromosome segregation; meiosis; polycomplex; synaptonemal complex.
Wesley ER, Hawley RS, Billmyre KK. [published ahead of print October 18 2020]. Chromosoma. 2020.
Experiments performed in different genetic backgrounds occasionally exhibit failure in experimental reproducibility. This is a serious issue in Drosophila where there are no standard control stocks. Here, we illustrate the importance of controlling genetic background by showing that the timing of a major meiotic event, the breakdown of the synaptonemal complex (SC), varies in different genetic backgrounds. We assessed SC breakdown in three different control stocks and found that in one control stock, y w; svspa-pol, the SC broke down earlier than in Oregon-R and w1118 stocks. We further examined SC breakdown in these three control backgrounds with flies heterozygous for a null mutation in c(3)G, which encodes a key structural component of the SC. Flies heterozygous for c(3)G displayed differences in the timing of SC breakdown in different control backgrounds, providing evidence ofa sensitizing effect of this mutation. These observations suggest that SC maintenance is associated with the dosage of c(3)G in some backgrounds. Lastly, chromosome segregation was not affected by premature SC breakdown in mid-prophase, consistent with previous findings that chromosome segregation isnot dependent on full-length SC in mid-prophase. Thus, genetic background is an important variable to consider with respect to SC behavior during Drosophila meiosis.
Genetic background; Meiosis; Synaptonemal complex.
Want to be an undergraduate intern in the Hawley Lab?
Emily Wesley, UMKC Undergraduate
Emily has worked as an Undergraduate Researcher in the Hawley Lab since January 2018, under the guidance of Dr. Katie Billmyre, a postdoctoral researcher. Recently, Emily completed a published project investigating how genetic background affected synaptonemal complex (SC)maintenance in Drosophila melanogaster. Surprisingly, the genetic background effect worsened when heterozygous for a c(3)G null allele (the transverse filament component of the SC). Additionally, she is working on characterizing a corolla mutant with three deletions in cyclin dependent kinase binding sites. Working as an intern in Dr. Hawley's lab has been an invaluable experience, allowing Emily to fully appreciate the process of scientific discovery. Being able to conduct independent experiments with terrific guidance and mentorship has fostered her curiosity and love of science. Emily would recommend the experience to others who are eager to become closely involved with the research process. She notes that she has gained an abundance of knowledge and skills that will continue to benefit her in a future career in biomedical science. Emily asserts that the Hawley Lab was the best place to begin her career in science and the experiences she has had will serve as a foundation for achieving future goals.
Danny Miller currently is a combined pediatrics and medical genetics resident at Seattle Children’s Hospital and the University of Washington. Clinically, he is interested in unsolved genetic disorders and how long-read sequencing might be used to both increase the rate of genetic diagnoses and decrease the amount of time it takes to make a genetic diagnosis
Working with Scott Hawley was a dream come true for Nicole. She has noted that she would not be the scientist she is today without the experience in his lab. She still uses genetics as her primary tool of research and is still studying the principles of cell division and meiosis, now as a postdoc. She is currently working as a postdoc at the University of Colorado in Julia Cooper's lab, studying fission yeast telomeres and centromeres. The training she received in the Hawley Lab, not only in scientific method and experimental procedures, such as microscopy and genetics, but generally as a scientist, have lasted her throughout her studies. She notes these skills and preparatory learning will continue to guide her in her future career. Scott taught her to think critically and how to mentor the future generations of scientists (and truly enjoy it), while instilling a love of meiosis, genetics, and science, in general.
Nazanin Yeganeh Kazemi
What we're reading
A sampling of recent literature of special interest to the Hawley Lab, with occasional comments from lab members.
Chromosome-autonomous feedback downregulates meiotic DNA break competence upon synaptonemal complex formation
Mu X, Murikami H, Mihibullah N, Keeney S. Genes Dev. 2020 Dec 1; 34(23-24): 1605-1618. doi: 10.1101/gad.342873.120. Epub 2020 Nov 12.
Crossover Position DrivesChromosome Remodeling for Accurate Meiotic Chromosome Segregation.
Altendorfer E, Láscarez-LagunasLI, Nadarajan S, Mathieson I, Colaiácovo MP. Curr Biol. 2020 Apr 6;30(7):1329-1338.e7. doi:10.1016/j.cub.2020.01.079. Epub 2020 Mar 5. PMID: 32142707.
"Within this paper may well lie the answer to the paradoxical excess of DSBs versus Cos, and maybe a reason the Inteference matters." –R Scott Hawley
Elevated Temperatures Cause Transposon-Associated DNA Damage in C. elegans Spermatocytes.
Kurhanewicz NA, Dinwiddie D, Bush ZD, Libuda DE. Curr Biol. 2020 Oct; 10:S0960-9822(20)31420-2. doi: 10.1016/j.cub.2020.09.050. Online ahead ofprint. PMID: 33065011. Free article.
Excess crossovers impede faithful meiotic chromosome segregation in C. elegans.
Hollis JA, Glover ML, Schlientz AJ, Cahoon CK, Bowerman B, Wignall SM, Libuda DE. PLoS Genet. 2020 Sep 4; 16(9):e1009001. doi:10.1371/journal.pgen.1009001. eCollection 2020 Sep. PMID: 32886661. Free PMC article.
Failure to recombine is a common feature of human oogenesis.
Hassold T, Maylor-Hagen H, Wood A, Gruhn J, Hoffmann E, Broman KW, Hunt P. Am J Hum Genet. 2020 Nov 24:S0002-9297(20)30407-9. doi: 10.1016/j.ajhg.2020.11.010. Epub ahead of print. PMID: 33306948.
Multivalent weak interactions between assembly units drive synaptonemal complex formation.
Zhang Z, Xie S, Wang R, Guo S, Zhao Q, Nie H, Liu Y, Zhang F, Chen M, Liu L, Meng X, Liu M, Zhao L, Colaiácovo MP, Zhou J, Gao J. J Cell Biol. 2020 May 4; 219(5):e201910086.doi: 10.1083/jcb.201910086. PMID: 32211900. Free article.
SCF-Fbxo42 promotes synaptonemal complex assembly by downregulating PP2A-B56.
Barbosa P, Zhaunova L, Debilio S, Steccanella V, Kelly V, Ly T, Ohkura H. J Cell Biol. 2021 Feb 1;220(2):e202009167. doi: 10.1083/jcb.202009167. PMID: 33382409.
Synaptonemal Complex Central Region Proteins Promote Localization of Pro-crossover Factors to Recombination Events During Caenorhabditiselegans Meiosis.
Cahoon CK, Helm JM, Libuda DE. Genetics. 2019 Oct; 213(2):395-409. doi:10.1534/genetics.119.302625. Epub 2019 Aug 20. PMID: 31431470. Free PMC article.
Quantitative cytogeneticsreveals molecular stoichiometry and longitudinalorganization of meiotic chromosome axes and loops.
Woglar A, Yamaya K, Roelens B, BoettigerA, Köhler S, Villeneuve AM. PLoS Biol. 2020 Aug 19; 18(8):e3000817. doi: 10.1371/journal.pbio.3000817. eCollection 2020 Aug. PMID: 32813728, Free PMC article.
Interested in becoming a member of the Hawley Lab?
For motivated undergraduates, please refer to the Undergraduate Research tab for information on how to become an intern in the lab.
Students with an interest in conducting their PhD thesis work in the Hawley Lab should apply through the Graduate School of the Stowers Institute for Medical Research. Doctoral students from other PhD programs should contact Dr. Hawley directly at firstname.lastname@example.org
Dr. Hawley is accepting applications for independent, ambitious postdoctoral scholars on a rolling basis. To apply, please send a current CV, a brief description of your doctoral research, and a paragraph summarizing what you are most interested in working upon joining the lab.
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