Education & Training
- Graduate School – Princeton University – PhD – Molecular Biology
- Post-Doctoral Fellowship – Carnegie Institution for Science - Embryology
NIH Grants: R01, R21
Each day, our genome is confronted with hundreds of insults that damage our DNA and must be repaired to ensure the proper functioning of 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: 1) pathways that control and monitor meiotic recombination, the exchange of DNA between maternal and paternal chromosomes, 2) pathway choice during DNA double-strand break repair and 3) general mechanisms of germ cell development and aging.
Chromosome segregation errors 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, a deeper understanding of these proteins may provide insights into both reproductive health, as well as cancer.
- Macaisne N, Kessler Z, Yanowitz JL. Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization. Genetics. 2018 Nov;210(3):843-856. doi: 10.1534/genetics.118.301402. Epub 2018 Sep 21. PubMed PMID: 30242011; PubMed Central PMCID: PMC6218235.
- Ahuja JS, Sandhu R, Mainpal R, Lawson C, Henley H, Hunt PA, Yanowitz JL, Börner GV. Control of meiotic pairing and recombination by chromosomally tethered 26S proteasome. Science. 2017 Jan 27;355(6323):408-411. doi: 10.1126/science.aaf4778. Epub 2017 Jan 5. PubMed PMID: 28059715; PubMed Centra PMCID: PMC6054871.
- McClendon TB, Mainpal R, Amrit FR, Krause MW, Ghazi A, Yanowitz JL. X Chromosome Crossover Formation and Genome Stability in Caenorhabditis elegans Are Independently Regulated by xnd-1. G3 (Bethesda). 2016 Dec 7;6(12):3913-3925. doi: 10.1534/g3.116.035725. PubMed PMID: 27678523; PubMed Central PMCID: PMC5144962.
- Machovina TS, Mainpal R, Daryabeigi A, McGovern O, Paouneskou D, Labella S, Zetka M, Jantsch V, Yanowitz JL. A Surveillance System Ensures Crossover Formation in C. elegans. Curr Biol. 2016 Nov 7;26(21):2873-2884. doi: 10.1016/j.cub.2016.09.007. Epub 2016 Oct 6. PubMed PMID: 27720619; PubMed Central PMCID: PMC5104180.
- Mateo AR*, Kessler Z*, Jolliffe AK, McGovern O, Yu B, Nicolucci A, Yanowitz JL, Derry WB&. The p53-like Protein CEP-1 Is Required for Meiotic Fidelity in C. elegans. Curr Biol. 2016 May 9;26(9):1148-58. doi: 10.1016/j.cub.2016.03.036. Epub 2016 Apr 14. PubMed PMID: 27151662; PubMed Central PMCID: PMC5215890. *contributed equally.
- McClendon TB*, Sullivan MR*, Bernstein KA, Yanowitz JL. Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans. Genetics. 2016 May;203(1):133-45. doi: 10.1534/genetics.115.185827. Epub 2016 Mar 2. PubMed PMID: 26936927; PubMed Central PMCID: PMC4858769. *contributed equally.