DNA strand break repair and human genetic disease.
Each day tens of thousands of DNA single-strand breaks (SSBs) arise in every cell from the attack of deoxyribose and DNA bases by reactive oxygen species and other electrophilic molecules. DNA double-strand breaks (DSBs) also arise, albeit at a much lower frequency, from similar attacks and from the encounter of unrepaired SSBs and possibly other DNA structures by DNA replication forks. DSBs are also created during normal development of the immune system. Defects in the cellular response to DNA strand breaks underpin many human diseases, including disorders associated with cancer predisposition, immune dysfunction, radiosensitivity, and neurodegeneration. Here we provide an overview of the genetic diseases associated with defects in the repair/response to DNA strand breaks.
McKinnon
Peter J
PJ
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Caldecott
Keith W
KW
D001072:Apraxias / Q000235:genetics; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004720:Endonucleases; D005199:Fanconi Anemia / Q000235:genetics; D019398:Genes, BRCA1 / Q000502:physiology; D024522:Genes, BRCA2 / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D000076228:MRE11 Homologue Protein; D008831:Microcephaly / Q000235:genetics; D049932:Nijmegen Breakage Syndrome / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
C438188:APTX protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C508551:NHEJ1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C426344:DCLRE1C protein, human; D004720:Endonucleases; D000076228:MRE11 Homologue Protein; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP