Education & Training
- Ph.D. in Molecular Biology-Princeton University 1999
- B.S. in Biology-MIT 1991
Research Interest Summary
Each day, our genome is confronted with hundreds of insults that damage our DNA and must be repaired to ensure the proper functioning our cells and the faithful segregation of our genetic material to the next generation. The work in the Yanowitz lab uses the nematode, Caenorhabditis elegans, to molecularly and genetically characterize the processes that maintain genome integrity in developing germ cells. The work is divided into three mains area of research, pathways the 1) control and 2) monitor crossing over, the exchange of DNA between maternal and paternal chromosomes, and 3) mechanisms of double-strand break repair.
Chromosome missegregation during the formation of egg and sperm are major causes of miscarriage and infertility. Further, greater than seventy percent of miscarriages arises from defects in meiotic crossover recombination. Our studies have identified proteins that control when, where and how many crossovers occur per chromosome. These studies provide insight into the etiology of human chromosome abnormalities by illuminating why some chromosomes are more susceptible to missegregation than others. These studies led us to identify a crossover surveillance system that ensures that each chromosome receives an exchange and delays development if they have not. Understanding how this system works may be exploited to identify oocytes that have properly executed all of the events of meiosis. Lastly, we have identified several key proteins that have dual roles in meiotic DNA repair and replicative repair, ensuring that meiotic exchanges and repair of double-strand breaks from genotoxic exposure are repaired with high fidelity. Thus, deeper understanding of these proteins may provide insights into both reproductive health, as well as cancer.
Wagner C, Kuervers L, Baillie D, and Yanowitz J. 2010. xnd-1 Regulates the Global Recombination Landscape in C. elegans. Nature, 467(7317):839-43. PMCID: PMC3045774
Meneely PM, McGovern OL, Heinis FI, and Yanowitz J. 2012. Crossover distribution and frequency is regulated by him-5 in C. elegans. Genetics Apr;190(4):1251-66. PMCID: PMC3316641
Kessler Z and Yanowitz J. 2014. Methodological considerations for mutagen exposure in C. elegans. Methods. Aug 1;68(3):441-9. Epub 2014 Apr 21. PMID: 24768858
Chung G, Rose AM, Petalcorin MI, Martin JS, Kessler Z, Sanchez-Pulido L, Ponting CP, Yanowitz JL*, Boulton SJ*. 2015 REC-1 and HIM-5 distribute meiotic crossovers and function redundantly in meiotic double-strand formation in Caenorhabditis elegans. Genes and Development Sep 15;29(18):1969-79. PMID: 26385965 *co-corresponding authors
Mainpal R. Nance J. Yanowitz JL. 2015. A germ cell determinant reveals parallel pathways for germ line development in Caenorhabditis elegans. Development Sept 22 pii: dev.125732 PMID: 26395476.
McClendon TB, Sullivan MR, Bernstein KA*, Yanowitz JL*. 2016. Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans. Genetics, advanced online publication, March 2, 2016. doi: 10.1534/genetics.115.185827. *co-corresponding authors.
Mateo A, Kessler ZK, Jolliffe K, McGovern O, Yu B, Nicolucci, A, Yanowitz JL*. and Derry WB*. 2016. The p53-like protein CEP-1 is required for meiotic fidelity in C. elegans. Current Biology, 26(9):1148-58. doi: 10.1016/ j.cub.2016.03.036. *co-corresponding authors.
Mainpal R and Yanowitz JL. 2016. A twist of fate: how a meiotic protein is providing new perspectives on germ cell development. Solicited manuscript, Worm, 5(2):e1175259. doi: 10.1080/21624054.2016.1175259.
Machovina T, Mainpal R, Daryabeigi A, McGovern O, Paouneskou D, Labella S, Zetka M, Jantsch V, and Yanowitz JL. 2016. A surveillance system ensures crossover formation in C. elegans. Current Biology, 26(21):2873-2884. doi: 10.1016/j.cub.2016.09.007.
McClendon TB, Mainpal R, Amrit FR, Krause MW, Ghazi A, and Yanowitz JL. 2016. X chromosome crossover formation and genome stability in Caenorhabditis elegans are independently regulated by xnd-1. G3, Oct 5. pii: g3.116.035725. doi: 10.1534/g3.116.035725