Ilya J. Finkelstein (abridged CV)

IJF

MBB 3.422
Dept. of Molecular Biosciences
University of Texas at Austin
Austin, TX 78712-1199
lab: 512-475-6172
website: https://finkelsteinlab.org
e-mail: ifinkelstein@cm.utexas.edu

Education

University of California, Berkeley (1997-2001)
B.S. Chemistry

Stanford University (2001-2007)
Ph.D. Chemistry
(thesis: ~4 MB PDF)

Professional Experience

Assistant Professor (2012-present)
Department of Molecular Biosciences,
Livestrong Cancer Institute,
Institute for Cellular and Molecular Biology,
Center for Systems and Synthetic Biology,
The University of Texas at Austin

Postdoctoral Fellow (2007-2012)
Columbia University Medical Center (with Eric C. Greene)

Graduate Student (2001-2007)
Stanford University (with Michael D. Fayer)

Awards and Honors

Five Significant Publications (from 45+)

We developed a chip-hybridized affinity mapping platform (CHAMP) that recycles used NGS chips for massively-parallel biophysical studies of protein-nucleic acid interactions. Using CHAMP, we uncovered novel proofreading activities of a Type I-E CRISPR system on both synthetic and genomic DNA. We anticipate that this method will be broadly applicable for biophysical studies of protein-nucleic acid interactions.

This manuscript identifies fission yeast as the first eukaryotic cell that appears not to age. This remarkable observation was made possible by a new microfluidic device that we developed for monitoring thousands of individual fission yeast cells over their entire replicative lifespans. We show for the first time that these cells die via aging-independent mechanisms (e.g., genome instability). Remarkably, the replicative lifespan can be extended via drugs and genetic perturbations, suggesting that longevity can be extended without necessarily slowing aging. This work establishes fission yeast as a powerful model organism for cellular aging.

Mammalian DNA breaks are identified by the Mre11/Rad50/Nbs1 (MRN) and Ku70/Ku80 (Ku) complexes. Ku directs repair towards error-prone non-homologous end joining, whereas MRN promotes error-free homologous recombination. Here, we describe how MRN: (1) rapidly locates free DNA ends, (2) removes Ku from these ends, and (3) initiates homologous recombination. This work provides a molecular view light on how human cells initiate DNA break repair.

Exonuclease 1 (Exo1) is a conserved eukaryotic nuclease that participates in DNA break repair, telomere maintenance, and mismatch repair. Here we examined Exo1 activity on DNA and in the presence of single-stranded DNA binding proteins using high-throughput single-molecule fluorescence imaging. We report that both human and yeast Exo1 are processive nucleases but are rapidly turned over by replication protein A (RPA). In the presence of RPA, Exo1 retains limited DNA-processing activity, albeit via a distributive binding mechanism. RPA-depleted human cells show elevated Exo1 loading but reduced overall DNA resection, underscoring the many roles of RPA in regulating DNA resection in vivo.

Post-replicative mismatch repair must identify rare DNA lesions (~1 mispair in 107-108 basepairs) in chromatin. Using single-molecule imaging, we demonstrate how two related eukaryotic mismatch sensors recognize these lesions on chromatin. Both factors can scan naked DNA, but only one of these complexes can also navigate on a chromatinized DNA substrate. This work begins to define the mechanisms of post-replicative mismatch repair on chromatin.

Recent Professional Activities

Updated August 8, 2018