An essential feature of living systems is their ability to rapidly and faithfully duplicate vast amounts of genetic information in preparation for cell division. DNA replication and repair are carried out by specialized molecular machines, and revealing how they function is critical to understand cell proliferation. Defects in replication and repair cause varied human diseases such as cancer, bone marrow failure, and neurodegeneration; uncovering how genome maintenance fails in human disease lays the foundation for new therapeutic interventions.
Egg extracts of the African frog Xenopus laevis (our vertebrate relative) contain the entire frog proteome and support virtually all aspects of genome maintenance. The extracts efficiently replicate added DNA templates, including ones containing damage, revealing how the replication machinery overcomes DNA lesions in the template strands. Replication and repair in extracts is regulated by phosphorylation and ubiquitin signaling, as seen in cells. We have used this system to discover previously unknown DNA repair pathways that are mutated in cancer (see Research). Single molecule imaging visualizes critical intermediates of replication and repair. In short, Xenopus egg extracts represent a “cell in a test tube” that allows mechanism- and discovery-based approaches in a physiological setting.
The Walter laboratory is a welcoming and highly interactive environment. Post-doctoral fellows and graduate students share reagents, expertise, and ideas to reach their common goal of understanding how cells replicate and repair DNA and how these processes go awry in human disease. We are always looking for energetic pre-doctoral students and accomplished post-doctoral fellows with expertise in molecular biology, biochemistry, and/or biophysics. Prior knowledge of Xenopus egg extracts is not required as incoming students and post-docs are trained in all relevant methods by current trainees. Walter lab alumni are successful in obtaining post-doctoral, industry, group leader, and other positions (see alumni).
Read on to learn more about current people and projects in the Walter lab.