Academic Appointments

Honors & Awards

  • Interdisciplinary Initiatives Program Seed Grant Award, Stanford BioX (2021-2023)
  • Postdoctoral Fellowship, Jane Coffin Childs Memorial Fund (2014-2017)
  • Outstanding Graduate Student Instructor Award, University of California, Berkeley (2008)
  • Silver Medal, International Physics Olympiad (2002)

Professional Education

  • Postdoctoral, Harvard Medical School, Biological Chemistry & Molecular Pharmacology (2019)
  • Ph.D., University of California, Berkeley, Physics (Biophysics) (2013)
  • M.A., University of California, Berkeley, Physics (Biophysics) (2012)
  • B.S., Massachusetts Institute of Technology, Physics (2007)

Contact

  • Academic
    University - Faculty Department: Chemical and Systems Biology Operations Position: Asst Professor

Additional Info

Links

Current Research and Scholarly Interests

Research in my laboratory is aimed at understanding how eukaryotes replicate their DNA despite numerous challenges (collectively known as replication stress), and more generally – how eukaryotic cells safeguard genome integrity. Specifically, we are investigating: (i) mechanisms that regulate the activity of the replicative helicase during replication stress, (ii) mechanisms that control the inheritance of epigenetic information during replication, and (iii) mechanisms of ubiquitin-mediated regulation of genome maintenance. We utilize single-molecule microscopy to directly image fluorescently-labeled replication factors and track them in real time in Xenopus egg extracts. I developed this system as a postdoctoral fellow, and used it to monitor how the eukaryotic replicative helicase copes with DNA damage. We plan to further extend the capabilities of this platform to directly visualize other essential replication factors, nucleosomes, and regulatory post-translational modifications like ubiquitin chains. By elucidating molecular mechanisms responsible for maintaining genome stability, we aim to better understand the link between genome instability and cancer, and how these mechanisms can be harnessed to improve disease treatment.

2023-24 Courses

Stanford Advisees

All Publications

  • Visualizing the dynamics of DNA replication and repair at the single-molecule level. Methods in cell biology Berger, S., Chistol, G. 2024; 182: 109-165

    Abstract

    During cell division, the genome of each eukaryotic cell is copied by thousands of replisomes-large protein complexes consisting of several dozen proteins. Recent studies suggest that the eukaryotic replisome is much more dynamic than previously thought. To directly visualize replisome dynamics in a physiological context, we recently developed a single-molecule approach for imaging replication proteins in Xenopus egg extracts. These extracts contain all the soluble nuclear proteins and faithfully recapitulate DNA replication and repair in vitro, serving as a powerful platform for studying the mechanisms of genome maintenance. Here we present detailed protocols for conducting single-molecule experiments in nuclear egg extracts and preparing key reagents. This workflow can be easily adapted to visualize the dynamics and function of other proteins implicated in DNA replication and repair.

    View details for DOI 10.1016/bs.mcb.2023.07.001

    View details for PubMedID 38359974

  • In silico protein interaction screening uncovers DONSON's role in replication initiation. Science (New York, N.Y.) Lim, Y., Tamayo-Orrego, L., Schmid, E., Tarnauskaite, Z., Kochenova, O. V., Gruar, R., Muramatsu, S., Lynch, L., Schlie, A. V., Carroll, P. L., Chistol, G., Reijns, M. A., Kanemaki, M. T., Jackson, A. P., Walter, J. C. 2023: eadi3448

    Abstract

    CMG (Cdc45-MCM2-7-GINS) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit "pre-Loading Complex" (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a vertebrate pre-LC containing GINS, TOPBP1, and DNA pol epsilon. Our evidence suggests that DONSON docks the pre-LC onto MCM2-7, delivering GINS to its binding site in CMG. A patient-derived DONSON mutation compromises CMG assembly and recapitulates microcephalic dwarfism in mice. These results unify our understanding of eukaryotic replication initiation, implicate defective CMG assembly in microcephalic dwarfism, and illustrate how in silico protein-protein interaction screening accelerates mechanistic discovery.

    View details for DOI 10.1126/science.adi3448

    View details for PubMedID 37590370

  • Single-strand DNA breaks cause replisome disassembly Molecular Cell Vrtis, K. B., Dewar, J. M., Chistol, G., Wu, R., Graham, T. G., Walter, J. C. 2021; 81 (6): 1309-18

    View details for DOI 10.1016/j.molcel.2020.12.039

  • The DNA replication fork suppresses CMG unloading from chromatin before termination Genes & Development Low*, E., Chistol*[@], G., Zaher, M. S., Kochenova, O. V., Walter[@], J. C. 2020; 34: 1534-45

    View details for DOI 10.1101/gad.339739.120

  • TRAIP is a master regulator of DNA interstrand crosslink repair Nature Wu, R. A., Semlow, D. R., Kamimae-Lanning, A. N., Kochenova, O. V., Chistol, G., Hodskinson, M. R., Amunugama, R., Sparks, J. L., Wang, M., Deng, L., Mimoso, C. A., Low, E., Patel, K. J., Walter, J. C. 2019; 567 (7747): 267–72

    View details for DOI 10.1038/s41586-019-1002-0

  • The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair Cell Sparks*, J. L., Chistol*, G., Gao, A. O., Räschle, M., Larsen, N. B., Mann, M., Duxin, J. P., Walter, J. C. 2019; 176 (1-2): 167-81.e21

    View details for DOI 10.1016/j.cell.2018.10.053

  • Mechanochemical coupling and bi-phasic force-velocity dependence in the ultra-fast ring ATPase SpoIIIE eLife Liu*, N., Chistol*, G., Cui, Y., Bustamante, C. 2018; 7

    View details for DOI 10.7554/eLife.32354

  • Two-subunit DNA escort mechanism and inactive subunit bypass in an ultra-fast ring ATPase eLife Liu*, N., Chistol*, G., Bustamante, C. 2015; 4

    View details for DOI 10.7554/eLife.09224

  • Single-Molecule Visualization of MCM2-7 DNA Loading: Seeing Is Believing Cell Chistol, G., Walter, J. C. 2015; 161 (3): 429-30

    View details for DOI 10.1016/j.cell.2015.04.006

  • Molecular watchdogs on genome patrol eLife Chistol, G., Walter, J. 2014; 3: e02854

    View details for DOI 10.7554/eLife.02854

  • Mechanical operation and intersubunit coordination of ring-shaped molecular motors: insights from single-molecule studies Biophysical Journal Liu*, S., Chistol*, G., Bustamante, C. 2014; 106 (9): 1844-58

    View details for DOI 10.1016/j.bpj.2014.03.029

  • A viral packaging motor varies its DNA rotation and step size to preserve subunit coordination as the capsid fills Cell Liu*, S., Chistol*, G., Hetherington*, C., Tafoya, S., Aathavan, K., Schnitzbauer, J., Grimes, S., Jardine, P. J., Bustamante, C. 2014; 157 (3): 702-13

    View details for DOI 10.1016/j.cell.2014.02.034

  • High degree of coordination and division of labor among subunits in a homomeric ring ATPase Cell Chistol*, G., Liu*, S., Hetherington, C. L., Moffitt, J. R., Grimes, S., Jardine, P. J., Bustamante, C. 2012; 151 (5): 1017-28

    View details for DOI 10.1016/j.cell.2012.10.031

  • ClpX(P) Generates Mechanical Force to Unfold and Translocate Its Protein Substrates Cell Maillard, R. A., Chistol, G., Sen, M., Righini, M., Tan, J., Kaiser, C. M., Hodges, C., Martin, A., Bustamante, C. 2011; 145 (3): 459-69

    View details for DOI 10.1016/j.cell.2011.04.010

https://orcid.org/0000-0003-4868-3667