THE ROLE OF DNA-REPAIR IN DEVELOPMENT

Several pathways of DNA repair are essential for maintaining genomic i ntegrity in mammalian cells, Mismatch repair is the final line of defe nse against polymerase errors during normal cellular replication. Base excision repair removes endogenous DNA damage resulting from normal c ellular metabolism, Nucleotide excision repair removes bulky, transcri ption blocking, lesions resulting from endogenous and environmental in sults to the DNA. The role of DNA repair in mammalian development is n ot well understood, Nevertheless, clues to the essential nature of the se processes are evident in the human DNA repair syndromes, in the nat ure of the interactions between DNA repair and other proteins, and in the phenotypes of genetically engineered, knockout mice lacking functi onal repair genes. Questions remain: what is the relative importance o f endogenous vs, environmental DNA damage and is repair itself critica l for normal development or are transcription-repair interactions more crucial? (C) 1997 Elsevier Science Inc.