Joseph Oberlitner, PhD
Dissecting crossover and non-crossovers DSB repair: from tagging RAD-51 to post-synaptic regulation
My thesis work focuses on characterizing double-strand repair in the germline during prophase I of meiosis of model nematode, šš¢š¦šÆš°š³š©š¢š£š„šŖšµšŖš“ š¦šš¦šØš¢šÆš“. DSB repair can be tracked through meiotic progression from the stem-cell niche to eventual oocytes. DSBs generated in the germline by meiotic recombination protein SPO-11 are repaired by homologous recombination, which has two sub-pathways: non-crossovers (NCOs) and crossovers (COs). Most DSBs are repaired using the non-crossover pathway but crossover repair is necessary for proper chromosome segregation. One of my main projects involves analyzing epitope tagged versions of DNA repair protein RAD-51 and how tagging can alter repair decisions of CO vs NCO repair. RAD-51 is used for homology search and strand invasion of repair templates in homologous recombination. Since both NCO and CO repair have distinct recombination intermediates, tagging RAD-51 may perturb one pathway more severely than the other. My other main project involves examining DNA damage resulting from the inability to remove DNA::RNA hybrids in the context of meiosis. Both RNase H1 and RNase H2 resolve DNA::RNA hybrids that form during transcription, in which the RNA transcript binds the single-stranded DNA behind RNA polymerase after being transcribed. If unresolved, DNA::RNA hybrids can lead to replication-transcription conflicts. These conflicts may result in collapsed replication forks, ultimately forming of a DSB. In C. elegans, combined loss of RNase H1 (ššāā1.0) and RNase H2 catalytic subunit (ššā-2), result in chromosomal fragmentation in the F2 generation as a result of irreparable DNA damage. š. š¦šš¦šØš¢šÆš“ has at least 3 other paralogs of RNase H1 (ššāā1.1, ššā-1.2, and ššā-1.3) though their role at present is unclear. Iām investigating these other paralogs and their roles in meiosis in the presence and absence of ššā-1.0 and ššā-2.
Honors/Awards:
Ballard & Seashore Dissertation Fellowship (Spring 2026)
Grad College Summer Fellowship (2025)
Poster Presenter*, FASEB Genetic Recombination and Genome Rearrangements Conference (2024)
Oral Presenter, 4th Chicago Area Worm Meeting (2023)
Poster Presenter, 22nd Midwest DNA Repair Symposium (2023)
*selected for oral teaser of poster