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Sara Di Rienzi

Joined Program: 2006
Previous Degree: B.A. Biology, Bryn Mawr College
Brewer-Raghuraman Lab
dirienzi (at) u.washington.edu

Research:
Origins of replication may be two-faced. As the genomic sites where DNA replication initiates, origins of replication are required for genome maintenance. However, accumulating evidence suggests that origins may be fragile sites inducing chromosomal rearrangements and local duplications—events linked to disease and cancer. In the Brewer-Raghuraman lab, I study the evolution of origins and their relationship to chromosomal breakpoints in the yeasts Saccharomyces cerevisiae and Kluyveromyces waltii. Saccharomyces diverged from Kluyveromyces via a whole genome duplication (WGD) event and subsequent gene loss, which returned the ploidy to nearly 1N. Consequently, each region in K. waltii (pre-WGD) is found in two syntenic S. cerevisiae regions (post-WGD) with complementary gene sets. In addition, chromosomal rearrangements occurred such that a given K. waltii chromosome is composed of blocks of genes rearranged on multiple S. cerevisiae chromosomes. Currently, I am mapping origins of replication in K. waltii by screening a K. waltii genomic library for Autonomously Replicating Sequences (ARSs), sequences capable of replicating a plasmid. After creating a library of ARSs, I will compare the sequence and density of K. waltii ARSs to S. cerevisiae ARSs. As well I will analyze the relationship of ARSs to the ancient breakpoints following the WGD event. To experimentally test for a role of origins in genome instability, I will be collaborating with Dr. Maitreya Dunham. In this collaboration, we will be looking for evidence that origin proximity is a factor in creating breakpoints leading to local gene duplications. Finally, I will be evaluating the degree of functional conservation of ARSs between S. cerevisiae and K. waltii through cross-species ARS library exchanges. Ultimately, I hope to begin to understand the evolution of replication origins and link origins to genome instability.