DNA damage processing defects and disease.

Abstract

Inherited defects in DNA repair or the processing of DNA damage can lead to disease. Both autosomal recessive and autosomal dominant modes of inheritance are represented. The diseases as a group are characterized by genomic instability, with eventual appearance of cancer. The inherited defects frequently have a specific DNA damage sensitivity, with cells from affected individuals showing normal resistance to other genotoxic agents. The known defects are subtle alterations in transcription, replication, or recombination, with alternate pathways of processing permitting cellular viability. Distinct diseases may arise from different mutations in one gene; thus, clinical phenotypes may reflect the loss of different partial functions of a gene. The findings indicate that partial defects in transcription or recombination lead to genomic instability, cancer, and characteristic disease phenotypes.