Recombomice: The past, present, and future of recombination-detection in mice

Homology directed repair (HDR) provides an efficient strategy for repairing and tolerating many types of DNA lesions, such as strand breaks. base damage. and crosslinks. Recombinational repair and lesion avoidance pathways that involve homology searching are integral to normal DNA replication. Indeed, it is estimated that at least ten HDR events take place each time a mammalian cell divides. HDR is associated with the transfer and exchange of DNA sequences. Usually, homologous sequences are aligned perfectly and flanking sequences are not exchanged. However, those sequence misalignments and exchanges that do occur can lead to rearrangements that contribute to cancer (e.g. deletions, inversions, translocations or loss of heterozygosity (LOH)). In order to reveal genetic and environmental factors that modulate HDR in mammals, several approaches have been used to detect recombination events in vivo. Here, we briefly review three methods for detecting homologous recombination in mice, namely: sister chromatid exchange (SCE), LOH, and recombination at tandem repeats. We conclude with a more detailed description of the recently developed "Fluorescent Yellow Direct Repeat" (FYDR) mouse model, which exploits enhanced yellow fluorescent protein (EYFP) for detecting mitotic homologous recombination in vivo. Applications of the FYDR mice are described, as well as the broader potential for using fluorescent proteins to detect recombination in various tissues/cell types in vivo. (C) 2004 Elsevier B.V. All rights reserved.