Dr. G. Valentin Boerner

Prominent changes in higher order chromosome organization occur in parallel with DNA transitions on the molecular level at all stages of the cell cycle. Coordination between these events is critical for the transmission of an intact genome. Defects in genome stability are associated with cancer, aging and birth defects such as Down syndrome.

We are investigating the interplay between chromosome structure and DNA recombination during meiosis. Meiosis is characterized by a series of well-defined transitions: During the prophase of meiosis I, homologous chromosomes undergo pairing, organize along proteinaeous axes, and become connected via the synaptonemal complex (SC). In parallel, recombination is initiated by introduction of numerous double strand breaks (DSBs) which are processed into crossovers. Crossovers establish a physical connection between homologous chromosomes thereby ensuring their faithful segregation.

Crossovers are non-randomly distributed along the genome, suggesting a mechanism of genome-wide coordination. We have previously shown that crossover sites become designated when the broken chromosome first interacts with its partner homolog (B?rner et al., 2004). This indicates that crossover sites are designated (i) prior to and independent of SC formation and (ii) at an earlier stage than predicted by classical models of homologous recombination. The ZMM group of proteins mediates both crossover-specific strand invasion and SC polymerization, suggesting functional linkage between these key events.

We are using cytological, biochemical and functional genomics approaches to analyze roles of the SC and SC-associated proteins in chromosomal exchange (Perry et al., 2005). We are further investigating the surveillance mechanisms that couple DSB processing to the progression of the meiotic cell cycle (B?rner, 2006).

Chriss A, B?rner GV, Ryan SD. (2024) Agent-based modeling of nuclear chromosome ensembles identifies determinants of homolog pairing during meiosis. PLoS Comput Biol. 20(5):e1011416.

B?rner GV, Hochwagen A, MacQueen AJ. (2023) Meiosis in budding yeast. Genetics 225(2):iyad125.

Sandhu R, Monge Neria F, Monge Neria J, Chen X, Hollingsworth NM & B?rner GV* (2020). DNA Helicase Mph1FANCM Ensures Meiotic Recombination between Parental Chromosomes by Dissociating Precocious Displacement Loops. Dev. Cell 18;53(4):458.

Sandhu R & B?rner GV* (2017). Meiosis: Stopping chromosomes from breaking bad.(Comment) eLife 6, pii: e27292.

Ahuja JS, Sandhu R, Mainpal R, Lawson C, Henley H, Hunt PA, Yanowitz JL & B?rner GV* (2017). Control of meiotic pairing and recombination by chromosomally tethered 26S proteasome. Science 355, 408-411.

Callender TL, Laureau R, Wan L, Chen X, Sandhu R, Laljee S, Zhou S, Suhandynata RT, Prugar E, Gaines WA, Kwon Y, B?rner GV, Nicolas A, Neiman AM & Hollingsworth NM (2016). Mek1 Down Regulates Rad51 Activity during Yeast Meiosis by Phosphorylation of Hed1. PLoS Genet. 12, e1006226.

Chen X, Suhandynata R, Sandhu R, Rockmill B, Mohibullah N, Niu H, Liang J, Lo H, Miller DE, Zhou H, B?rner GV & Hollingsworth NM (2015). Phosphorylation of the synaptonemal complex protein Zip1 by Cdc7-Dbf4 (DDK) regulates the crossover/ noncrossover decision during yeast meiosis. PLoS Biol. 13, e1002329.

B?rner GV* & Cha RS* (2015). Analysis of Recombination and Chromosome Structure during Yeast Meiosis. In Cold Spring Harb. Protoc. Ed.: Boone C 10:pdb.prot085050.

Joshi, N., Brown, M.S., Bishop, D.K. & B?rner, G.V.* (2015) Gradual implementation of the meiotic recombination program via checkpoint pathways controlled by global DSB levels. Mol. Cell 57:797-811.

Ahuja, J.S. & B?rner, G.V.* (2011) Analysis of meiotic recombination intermediates by two-dimensional gel electrophoresis. Methods Mol Biol. 745:99-116.

Joshi, N., Barot, A., Jamison, C. & B?rner, G.V.* (2009) Pch2 links chromosome axis remodeling at future crossover sites and crossover distribution during yeast meiosis. PLoS Genet. 5(7):e1000557.

B?rner, G.V., Barot, A., & Kleckner, N. (2008) Yeast Pch2 promotes domainal axis organization, timely recombination progression and arrest of defective recombinosomes during meiosis. Proc. Natl. Acad. Sci. USA 105:3327-3332.

Lynn A., Soucek R., & B?rner, G.V.* (2007) The ZMM proteins: Crossover artists at work. Chromosome Research 15, 591-605.

B?rner G.V.* (2006)  Balancing the checks: surveillance of chromosomal exchange during meiosis.  Biochem. Soc. Trans. 34:554-556.

Perry J., Kleckner N., & B?rner G.V. (2005) Bioinformatic analyses implicate three collaborating meiotic crossover/chiasma-implementing proteins, Zip2, Zip3 and Spo22/Zip4, in ubiquitin labeling.  Proc. Natl. Acad. Sci. USA 102:17594-17599.

B?rner G.V., Kleckner N. & Hunter N. (2004) Crossover/noncrossover differentiation, synaptonemal complex formation and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117:29-45.

Hunter N., B?rner G.V., Lichten M. & Kleckner N. (2001) Gamma-H2AX illuminates meiosis. Nature Genet. 27, 236-238.

B?rner G.V.*, Zeviani M., Tiranti V., Carrara F., Hoffmann S., Gerbitz K.D., Lochm¨¹ller H., Pongratz D., Klopstock T., Melberg A., Holme E. & P??bo S. (2000) Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients. Hum. Mol. Genet. 9, 467-475.

B?rner G.V., Yokobori S., M?rl M., D?rner M., & P??bo S. (1997) RNA editing in metazoan mitochondria: staying fit without sex. FEBS Letters 409, 320-324.

B?rner G.V. & P??bo S. (1996) Evolutionary fixation of RNA editing. Nature 383, 225.

B?rner G.V., M?rl M., Janke A., & P??bo S. (1996) RNA editing changes the identity of a mitochondrial tRNA in marsupials. EMBO J. 15:5949-5957.

Niemer I., Schmelzer C., & B?rner G.V.* (1995) Overexpression of DEAD box protein pMSS116 promotes ATP-dependent splicing of a yeast group II intron in vitro.  Nucleic Acids Res. 23:15:2966-72.

B?rner G.V.*, M?rl M., Wissinger B., Brennicke A., & Schmelzer C. (1995) RNA editing of a group II intron in Oenothera as a prerequisite for splicing. Mol. Gen. Genet. 246:739-744.

* corresponding author