Preserving the sequence and structure of the genetic material is crucial for an organisms function. Failure to maintain integrity of the genome can alter cellular function, leading to senescence, cancer, and heritable genetic mutations. Fortunately, our cells are armed with an arsenal of molecular machines that regulate DNA metabolism as well as detect and repair damage.
Our lab focuses in two key ways that eukaryotic cells maintain genome integrity so we can better understand how these processes work and what to do when they go wrong.
To ensure growth, tissue maintenance, and reproduction, cells must replicate their genome and pass this genetic information to new cells. Molecular machines regulate each replication stage and correct errors to maintain fidelity. Our lab studies Replication Protein A (RPA), a key protein that binds single-stranded DNA during replication. RPA regulates DNA polymerases and interacts with DNA repair enzymes. We aim to uncover how RPA orchestrates these processes to maintain genome integrity during replication.
Telomeres are protective structures at chromosome ends that shorten each time a cell divides, due to an inability of the replication machinery to fully replicate to the ends of linear chromosomes. The enzyme telomerase counteracts this shortening, and failure to maintain telomere length ultimately resulting in cellular senescence or cell death. Mutations in telomere-length regulation genes cause severe degenerative disease in humans. Our lab investigates how single-stranded DNA-binding proteins regulate telomere replication and telomerase activity.
Also known as brewers yeast or bakers yeast, Saccharomyces cerevisiae has served as a model organism for decades, revealing many fundamental pathways in cellular and molecular biology. The molecular machinery governing genome integrity are conserved between yeast and humans, allowing us to use this tractable organism to model patient mutations and discover how our cells protect their genomes.