Genomic instability and cancer: networks involved in response to DNA damage.
A new approach to cancer and new methods in examining rare human chromosome breakage syndromes have brought to light complex interactions between different pathways involved in damage response, cell cycle checkpoint control and DNA repair. The genes affected in these different syndromes are involved in networks of processes that respond to DNA damage and prevent chromosomal aberrations during the cell cycle. The genes involved include the ATM, ATR, FA-associated genes, NBS1 and the cancer susceptibility genes BRCA1 and BRCA2. Chromosomal instability is a common feature of many human cancers and most of the instability syndromes, characterized by sensitivity to different types of DNA damage, also show increased cancer susceptibility. Better understanding of these syndromes and their links with familial cancer provide new insight into associations between defects in DNA damage response, cell cycle control, DNA repair and cancer. Understanding the damage response repair networks that these studies are revealing will have important implications for the development of cancer management and treatment.
Faculty of Medicine, University of Iceland, Icelandic Cancer Society, 105 Reykjavik, Iceland. jorunn@krabb.is
Jorunn Erla
JE
Eyfjord
Sigridur Klara
SK
Bodvarsdottir
D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002874:Chromosome Mapping; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D042822:Genomic Instability; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016615:Telomere / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases