title: Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation.
abstract: Cockayne syndrome (CS) is a rare human disorder characterized by pathologies of premature aging, neurological abnormalities, sensorineural hearing loss and cachectic dwarfism. With recent data identifying CS proteins as physical components of mitochondria, we sought to identify protein partners and roles for Cockayne syndrome group B (CSB) protein in this organelle. CSB was found to physically interact with and modulate the DNA-binding activity of the major mitochondrial nucleoid, DNA replication and transcription protein TFAM. Components of the mitochondrial transcription apparatus (mitochondrial RNA polymerase, transcription factor 2B and TFAM) all functionally interacted with CSB and stimulated its double-stranded DNA-dependent adenosine triphosphatase activity. Moreover, we found that patient-derived CSB-deficient cells exhibited a defect in efficient mitochondrial transcript production and that CSB specifically promoted elongation by the mitochondrial RNA polymerase in vitro. These observations provide strong evidence for the importance of CSB in maintaining mitochondrial function and argue that the pathologies associated with CS are in part, a direct result of the roles that CSB plays in mitochondria.
authors: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors: Brian R
authors: BR
authors: Berquist
authors: Chandrika
authors: C
authors: Canugovi
authors: Peter
authors: P
authors: Sykora
authors: David M
authors: DM
authors: Wilson
authors: Vilhelm A
authors: VA
authors: Bohr
mesh_terms: D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; D004247:DNA; D008780:Methyltransferases; C462443:TFB2M protein, human; D012321:DNA-Directed RNA Polymerases; C519567:POLRMT protein, human; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes