Honors & Awards


  • Honorable Mention, NSF GRFP (2015)

Education & Certifications


  • B.A., University of California, Berkeley (2011)

Stanford Advisors


Work Experience


  • Staff Research Associate, Toczyski Lab, UCSF (March 2012 - August 2014)

    Location

    San Francisco, CA

All Publications


  • Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein's C-Terminal Helix MOLECULAR CELL Topacio, B. R., Zatulovskiy, E., Cristea, S., Xie, S., Tambo, C. S., Rubin, S. M., Sage, J., Koivomagi, M., Skotheim, J. M. 2019; 74 (4): 758-+
  • Cyclin D-Cdk4,6 Drives Cell-Cycle Progression via the Retinoblastoma Protein's C-Terminal Helix. Molecular cell Topacio, B. R., Zatulovskiy, E., Cristea, S., Xie, S., Tambo, C. S., Rubin, S. M., Sage, J., Koivomagi, M., Skotheim, J. M. 2019

    Abstract

    The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein Rb, which inhibits cell-cycle progression until its inactivation by phosphorylation. However, the role of Rb phosphorylation by cyclin D-Cdk4,6 in cell-cycle progression is unclear because Rb can be phosphorylated by other cyclin-Cdks, and cyclin D-Cdk4,6 has other targets involved in cell division. Here, we show that cyclin D-Cdk4,6 docks one side of an alpha-helix in theRb C terminus, which is not recognized by cyclins E, A, and B. This helix-based docking mechanism is shared by the p107 and p130 Rb-family members across metazoans. Mutation of the Rb C-terminal helix prevents its phosphorylation, promotes G1 arrest, and enhances Rb's tumor suppressive function. Our work conclusively demonstrates that the cyclin D-Rb interaction drives cell division and expands the diversity of known cyclin-based protein docking mechanisms.

    View details for PubMedID 30982746

  • DNA Damage Regulates Translation through beta-TRCP Targeting of CReP PLOS GENETICS Loveless, T. B., Topacio, B. R., Vashisht, A. A., Galaang, S., Ulrich, K. M., Young, B. D., Wohlschlegel, J. A., Toczyski, D. P. 2015; 11 (6)

    Abstract

    The Skp1-Cul1-F box complex (SCF) associates with any one of a number of F box proteins, which serve as substrate binding adaptors. The human F box protein βTRCP directs the conjugation of ubiquitin to a variety of substrate proteins, leading to the destruction of the substrate by the proteasome. To identify βTRCP substrates, we employed a recently-developed technique, called Ligase Trapping, wherein a ubiquitin ligase is fused to a ubiquitin-binding domain to "trap" ubiquitinated substrates. 88% of the candidate substrates that we examined were bona fide substrates, comprising twelve previously validated substrates, eleven new substrates and three false positives. One βTRCP substrate, CReP, is a Protein Phosphatase 1 (PP1) specificity subunit that targets the translation initiation factor eIF2α to promote the removal of a stress-induced inhibitory phosphorylation and increase cap-dependent translation. We found that CReP is targeted by βTRCP for degradation upon DNA damage. Using a stable CReP allele, we show that depletion of CReP is required for the full induction of eIF2α phosphorylation upon DNA damage, and contributes to keeping the levels of translation low as cells recover from DNA damage.

    View details for DOI 10.1371/journal.pgen.1005292

    View details for Web of Science ID 000357341600040

    View details for PubMedID 26091241

    View details for PubMedCentralID PMC4474599

  • Hst3 is turned over by a replication stress-responsive SCFCdc4 phospho-degron PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Edenberg, E. R., Vashisht, A. A., Topacio, B. R., Wohlschlegel, J. A., Toczyski, D. P. 2014; 111 (16): 5962-5967

    Abstract

    Hst3 is the histone deacetylase that removes histone H3K56 acetylation. H3K56 acetylation is a cell-cycle- and damage-regulated chromatin marker, and proper regulation of H3K56 acetylation is important for replication, genomic stability, chromatin assembly, and the response to and recovery from DNA damage. Understanding the regulation of enzymes that regulate H3K56 acetylation is of great interest, because the loss of H3K56 acetylation leads to genomic instability. HST3 is controlled at both the transcriptional and posttranscriptional level. Here, we show that Hst3 is targeted for turnover by the ubiquitin ligase SCF(Cdc4) after phosphorylation of a multisite degron. In addition, we find that Hst3 turnover increases in response to replication stress in a Rad53-dependent way. Turnover of Hst3 is promoted by Mck1 activity in both conditions. The Hst3 degron contains two canonical Cdc4 phospho-degrons, and the phosphorylation of each of these is required for efficient turnover both in an unperturbed cell cycle and in response to replication stress.

    View details for DOI 10.1073/pnas.1315325111

    View details for Web of Science ID 000334694000057

    View details for PubMedID 24715726

    View details for PubMedCentralID PMC4000829