The role of DNA repair in development.

Several pathways of DNA repair are essential for maintaining genomic integrity in mammalian cells. Mismatch repair is the final line of defense against polymerase errors during normal cellular replication. Base excision repair removes endogenous DNA damage resulting from normal cellular metabolism. Nucleotide excision repair removes bulky, transcription blocking, lesions resulting from endogenous and environmental insults to the DNA. The role of DNA repair in mammalian development is not well understood. Nevertheless, clues to the essential nature of these processes are evident in the human DNA repair syndromes, in the nature of the interactions between DNA repair and other proteins, and in the phenotypes of genetically engineered, knockout mice lacking functional repair genes. Questions remain: what is the relative importance of endogenous vs. environmental DNA damage and is repair itself critical for normal development or are transcription-repair interactions more crucial?