Bonny Brewer
Professor of Genome Sciences
Research
I have been in love with DNA for as long as I can remember. I chose to study replication because it is central to the biological role of DNA as the molecule of inheritance, and I found in Baker’s yeast the perfect organism to investigate this fundamental process.
Research is conducted in collaboration with Professor M. K. Raghuraman (Raghu). We are studying the regulation of replication that ensures that each chromosome is duplicated in a timely and precise way, and are characterizing the consequences for chromosomes when these processes go awry. Although the chromosomes of the budding yeast are orders of magnitude smaller than those of plants and animals, they are organized for replication in much the same way: replication occurs from multiple, closely-spaced origins and different parts of a chromosome are replicated at different times during the S phase of the cell cycle, using machinery that is conserved from yeast to humans. Thus, studying how this small organism replicates and maintains its chromosomes gives us insights into how the same processes occur—or go awry—in our own cells.
Nearly 50 years ago, we pioneered the use of 2-dimensional gel electrophoresis techniques to map specific replication origins and to determine the efficiency with which they are activated. In the early days of DNA microarrays we developed methods and algorithms to study replication on a genome wide scale. While we now also use DNA sequencing to answer some questions about genome structure and replication, we find gels and Southern hybridization are often still the best tools to answer the questions that interest us.
While this work continues, in collaborations with Maitreya Dunham’s lab, we are also exploring the changes to chromosomes that occur during laboratory evolution and replicative aging and find they are often the consequence of an error in replication. Growing yeast cells continuously for many weeks in chemostats limiting for sulfur invariably results in the amplification of the gene that encodes the primary sulfate transporter, SUL1. While that outcome itself isn’t that surprising, the mechanisms that cells use to bring about the amplification are novel. The primary form of amplicon of the SUL1 gene and its adjacent origin of replication is a triplicated chromosomal fragment with the center copy in an inverted orientation. We proposed that an error in replication fork progressions explains how this particular structure is generated. When we interfere with this mechanism by mutating different genes involved in DNA replication or chromosome maintenance, we uncovered other mechanisms that cells use to achieve the selective benefits from SUL1 amplification. Structures similar to the yeast SUL1 amplicons have been found in humans where they are often associated with genetic disorders. We have also used chemostats to explore genomic changes that occur during aging of yeast cells. We propose that aberrant repair of broken replication forks generates branched chromosomes that cannot be properly segregated at division—thereby limiting yeast’s life span. Might these errors also be contributing to human aging? Stay tuned!
Selected Publications
Brewer, B. J. and W. L. Fangman (1987). “The localization of replication origins on ARS plasmids in S. cerevisiae.” Cell 51(3): 463-471; https://doi.org/10.1016/0092-8674(87)90642-8.
Raghuraman, M. K., E. A. Winzeler, D. Collingwood, S. Hunt, L. Wodicka, A. Conway, D. J. Lockhart, R. W. Davis, B. J. Brewer and W. L. Fangman (2001). “Replication dynamics of the yeast genome.” Science 294(5540): 115-121; https://doi.org/10.1126/science.294.5540.115.
Brewer, B. J., C. Payen, M. K. Raghuraman and M. J. Dunham (2011). “Origin-dependent inverted-repeat amplification: a replication-based model for generating palindromic amplicons.” PLoS Genet 7(3): e1002016; https://pmc.ncbi.nlm.nih.gov/articles/PMC3060070.
Sanchez, J. C., A. Ollodart, C. R. L. Large, C. Clough, G. M. Alvino, M. Tsuchiya, M. Crane, E. X. Kwan, M. Kaeberlein, M. J. Dunham, M. K. Raghuraman and B. J. Brewer (2019). “Phenotypic and Genotypic Consequences of CRISPR/Cas9 Editing of the Replication Origins in the rDNA of Saccharomyces cerevisiae.” Genetics 213(1): 229-249; https://pmc.ncbi.nlm.nih.gov/articles/PMC6727806.
Kwan, E. X., G. M. Alvino, K. L. Lynch, P. F. Levan, H. M. Amemiya, X. S. Wang, S. A. Johnson, J. C. Sanchez, M. A. Miller, M. Croy, S. B. Lee, M. Naushab, A. Bedalov, J. T. Cuperus, B. J. Brewer, C. Queitsch and M. K. Raghuraman (2023). “Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.” Cell Rep 42(3): 112161; https://pmc.ncbi.nlm.nih.gov/articles/PMC10142053.
Brewer, B. J., M. J. Dunham and M. K. Raghuraman (2024). “A unifying model that explains the origins of human inverted copy number variants.” PLoS Genet 20(1): e1011091; https://pmc.ncbi.nlm.nih.gov/articles/PMC10766186.
Brewer, B.J., R. Martin, E. Ramage, C. Payen, S. C. Di Rienzi, Y. Zhao, K. Van Sickle, J. I. Verhey, M. Zalusky, D. E. Miller, D., G. T. Ong, J. L. McKee, G. M. Alvino, M. J. Dunham and M. K. Raghuraman (2026). “Telomeric amplicons of SUL1 and Y’ in yeast are generated by microhomology-mediated break induced replication occurring in cis.” PLoS Genetics, in minor revision. https://doi.org/10.64898/2026.04.07.716220. Submitted April 17, 2026
Armstrong, J. O., E. X. Kwan, G. M. Alvino, M. K. Raghuraman, M. J. Dunham and B. J. Brewer. (2026) “Beyond ERCs: exploring catastrophic forms of rDNA instability in aging yeast.” PLoS Genetics, under review. https://doi.org/10.64898/2026.04.21.719800. Submitted April 18, 2026