In healthy cells, two major mechanisms prevent the propagation cells with abnormal chromosome content: the DNA damage response and the spindle checkpoint. Errors in DNA repair/recombination and chromosome segregation can result in infertility, tumorigenesis or developmental defects.
Much remains to be discovered about how chromosome stability is controlled at the molecular level. For instance, how much cell-to-cell or patient-to-patient variation is there in the type and frequency of DNA rearrangements? What puts certain genomic areas at risk for germline rearrangements? How does the cell sense and correct aberrant chromosome behavior, and if necessary, abandon correction attempts and initiate apoptosis (programmed cell death)?
We address these questions by examining in vivo outcomes of recombination-based DNA repair and chromosome segregation in mammalian meiosis and mitosis, by applying sensitive allele-specific PCR methods, genetics, immuno-FISH microscopy and functional DNA damage/repair assays. We aim to understand how cells repair broken DNA, and how they sense misbehaving chromosomes. These fundamental processes are essential for the maintenance of normal DNA content, and thereby normal gene dosage and cell function.