Retrotransposon repression in the germline

A major challenge faced by germ cells is the potential mutagenic activity of transposable genetic elements, which make up approximately half of mouse and human genomes. Uncontrolled transposon activity in the germline not only facilitates their vertical transmission, but also threatens genome integrity and germ cell viability. Germ cells employ multiple defense mechanisms to battle transposons, including transcriptional silencing by heritable DNA methylation and through specialized small RNAs known as piRNAs.

Our original screen for mouse meiotic mutants generated novel point-mutated alleles of numerous genes involved in the piRNA pathway. We also isolated a mutant allele of the recently discovered DNA methyltransferase, Dnmt3c, which mimics a mutation found in a Dnmt3b DNA methyltransferase-related human disorder. We are using this collection of mutants as tools to dissect transposon suppression mechanisms and study their interplay. We are also interested in how retrotransposon suppression intersects with other critical events during gametogenesis, such as meiotic recombination and chromosome synapsis.