title: Cockayne syndrome group B (CSB) protein: at the crossroads of transcriptional networks.
abstract: Cockayne syndrome (CS) is a rare genetic disorder characterized by a variety of growth and developmental defects, photosensitivity, cachectic dwarfism, hearing loss, skeletal abnormalities, progressive neurological degeneration, and premature aging. CS arises due to mutations in the CSA and CSB genes. Both gene products are required for the transcription-coupled (TC) branch of the nucleotide excision repair (NER) pathway, however, the severe phenotype of CS patients is hard to reconcile with a sole defect in TC-NER. Studies using cells from patients and mouse models have shown that the CSB protein is involved in a variety of cellular pathways and plays a major role in the cellular response to stress. CSB has been shown to regulate processes such as the transcriptional recovery after DNA damage, the p53 transcriptional response, the response to hypoxia, the response to insulin-like growth factor-1 (IGF-1), transactivation of nuclear receptors, transcription of housekeeping genes and the transcription of rDNA. Some of these processes are also affected in combined XP/CS patients. These new advances in the function(s) of CSB shed light onto the etiology of the clinical features observed in CS patients and could potentially open therapeutic avenues for these patients in the future. Moreover, the study of CS could further our knowledge of the aging process.
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/Université de Strasbourg, BP 163, 67404 Illkirch Cedex, C. U. Strasbourg, France. rvelez@mdanderson.org
authors.forename: Renier
authors.initials: R
authors.lastname: Vélez-Cruz
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Egly
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C490652:Ckn1 protein, mouse; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D004265:DNA Helicases; C078673:ERCC6 protein, human; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes