A synopsis of our research is given below, with links to more detailed information. Non-specialists should refer to the Research Synopsis for Poets and Connections to the Real World pages.

We study mechanisms and regulation of genetic recombination in different contexts. In the case of meiotic recombination, DNA double-strand breaks (DSBs) are induced to promote high rates of crossing over between homologous chromosomes; these crossovers prmote accurate disjunction and increase diversity among offspring.

In contrast, mitotic recombination is usually a response to an abnormal event, such as a broken replication fork, a transpoable element excision, or experimental introduction of Cas9. Repair is typically biased to prevent crossover formation, as crossovers can lead to loss of heterozygosity or chromosome rearragement, events that are associated with tumorigenesis.

These considerations lead to a key question that runs through much of our research:

Approaches we use include:

• Functional studies of genes and proteins involved in promoting or preventing crossovers:
  • anti-crossover helicases, such as BLM, FANCM, and MARCAL1
  • pro-crossover resolvases: Mei-9.com, GEN, Mus81-Mms4, and Mus312-Slx1
  • anti-anti-crossover proteins, namely the mei-MCM complex
• Molecular analysis of recombination mechanism, as in these assays:
  • gap repair assays that provide insights into SDSA and CRISPR/Cas9 engineering
  • mismatch repair mutants that preserve strand information from meiotic recombination intermediates
• Mechanistic analyses of processes that lead to non-random crossover distribution in:
  • meiosis (the centromere effect, interference, and assurance)
  • mitotic cells (e.g., fragile sites)