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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2013)

DNA replication timing, chromatin state and transcriptional activity of a genomic locus are tightly correlated and undergo vast changes during cell fate changes underlying differentiation and reprogramming processes. It has been proposed that the correlation of replication timing and transcriptional activity is mediated by the interaction of pre-replication complex (preRC) components with the transcription machinery. We addressed this question by investigating the influence of preRC components on transcriptional activity in embryonic stem cells (ESCs) by depleting components of the preRC. Interestingly, we did not find a global change of transcriptional activity. In addition, we tested the interaction of the preRC with the COMPASS chromatin modification complex. Contrary to results in the yeast system, we found no interaction between preRC components and the COMPASS complex in mouse ESCs do, and thus the recruitment of the preRC to origins of replication via this interacton is unlikely.

As the replication fork clamp proliferacting cell nuclear antigen (PCNA) is conveniently located at the replication fork and has a plethora of interaction partners, including a number of chromatin-modifying enzymes, PCNA might mediate the replication of chromatin states by recruiting chromatin-modifying enzymes to the replication fork at appropriate times during S-phase. We addressed this hypothesis by determining the PCNA interactome in unsynchronized ESCs as well as ESCs specifically in early or late S-phase, respectively, and identified a number of chromatin-modifying complexes as PCNA interactors some of which interacted specifically in early or late S-phase, supporting our model.

Interestingly, among the PCNA interaction partners identified, we found the annealing helicase Zinc finger Ran domain containing protein 3 (Zranb3), which we found to be particularly highly expressed in ESC. We further investigated the function of Zranb3 and identified the MutSalpha complex of the DNA mismatch repair machinery (MMR), a process especially upregulated in ESC, as interactor of Zranb3. Given the interaction of Zranb3 with the MutSalpha complex as well as PCNA and its high levels in ESCs, we suggest a model in which MutSalpha; recruits PCNA to sites of MMR and both are then bound by Zranb3 to repair DNA lesions.

  • 1 supplemental file
Cover page: Proteomic and transcriptional analysis of components of the DNA replication and repair machinery in mouse embryonic stem cells
  • Article
  • Peer Reviewed
UC Berkeley Previously Published Works (2021)
Low persistence in science majors and limited participation in high-impact research experiences contribute to the nationwide underrepresentation of minorities in the science workforce, particularly jobs requiring a graduate degree. The Program for Excellence in Education and Research in the Sciences (PEERS) is an academic support program at the University of California, Los Angeles (UCLA) that supports first- and second-year science majors from underrepresented and underserved backgrounds to maximize student success and science, technology, engineering, and mathematics (STEM) persistence. Here, we evaluate the success of PEERS through data from the UCLA registrar, student surveys, and longitudinal tracking of student outcomes. Results show that PEERS students have significantly higher participation rates in undergraduate research, despite PEERS having no formal research component. Importantly, PEERS students were seven times as likely to enroll in PhD programs, and twice as likely to enroll in MD programs compared with propensity-matched controls. Combined results show that increased success of PEERS students in their first 2 years as science majors resulted in improved outcomes later in their undergraduate studies and had tangible impacts on subsequent educational trajectories that will increase participation of underrepresented groups in high-skill STEM careers.
    Cover page: A Unique and Scalable Model for Increasing Research Engagement, STEM Persistence, and Entry into Doctoral Programs.
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