Requirement of Yeast RAD2, a Homolog of Human XPG Gene, for Efficient RNA Polymerase II Transcription

Sealy Center for Molecular Science, University of Texas Medical Branch, 6.104 Blocker Medical Research Building, 11th and Mechanic Streets, Galveston, TX 77555, USA.
Cell (Impact Factor: 33.12). 07/2002; 109(7):823-34. DOI: 10.1016/S0092-8674(02)00795-X
Source: PubMed

ABSTRACT In addition to xeroderma pigmentosum, mutations in the human XPG gene cause early onset Cockayne syndrome (CS). Here, we provide evidence for the involvement of RAD2, the S. cerevisiae counterpart of XPG, in promoting efficient RNA polymerase II transcription. Inactivation of RAD26, the S. cerevisiae counterpart of the human CSB gene, also causes a deficiency in transcription, and a synergistic decline in transcription occurs in the absence of both the RAD2 and RAD26 genes. Growth is also retarded in the rad2 Delta and rad26 Delta single mutant strains, and a very severe growth inhibition is seen in the rad2 Delta rad26 Delta double mutant. From these and other observations presented here, we suggest that transcriptional defects are the underlying cause of CS.

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    • "These results indicate that RAD2 and RAD26 provide alternate means for efficient transcription, and further, they implicate transcriptional defects as the underlying cause of growth impairment that occurs in the rad2Δ, rad26Δ, and rad2Δ rad26Δ mutant strains under conditions that would require the synthesis of new mRNAs. From these studies, they infer that CS is likely a transcription syndrome and that growth and developmental defects in CS could result from defects in transcription (Lee et al, 2002). In a report studying the involvement of CSB in RNA polymerase I transcription, functional XPG was identified in a complex with CSB, TFIIH, RNA polymerase I initiation factor TIF-IB and RNA polymerase I indicating that XPG might play a role in ribosomal transcription by RNA polymerase I (Bradsher et al, 2002). "
    DNA Repair and Human Health, 10/2011; , ISBN: 978-953-307-612-6
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    • "XPG is expected to have additional stabilization features, because of its ability to interact with XPB, XPD and several other subunits of the TFIIH complex(Friedberg et al.,2006b). Since loss of XPG results in very early death(Wijnhoven et al.,2007) the protein might be involved in systemic and important additional mechanisms, like transcription (Bessho,1999; Lee et al.,2002). Furthermore, XPG is suggested to have a role in oxidative damage removal (Dianov et al.,2000). "
    DNA Repair and Human Health, 10/2011; , ISBN: 978-953-307-612-6
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    • "How certain mutations in XPG would fit within that paradigm has not been obvious. Roles for XPG in transcription [16] and the repair of oxidative DNA damage have been suggested to contribute to the CS phenotype, but the importance of the latter connection in particular is still uncertain [26]. The recent study from the Tanaka and Egly laboratories has provided a possible answer to this question and might provide an explanation for the XP/CS phenotype in more general terms [21]. "
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    ABSTRACT: Alterations in genes involved in nucleotide excision repair (NER) are associated with three genetic disorders, xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). The transcription and repair factor TFIIH is a central component of NER and mutations of its subunits are associated with all three diseases. A recent report provides a molecular basis for how mutations in the NER endonuclease XPG that affect the interaction of TFIIH might give rise to CS features. In cells of XP-G patients with a combined XP and CS phenotype, XPG fails to associate with TFIIH and as a consequence the CAK subunit dissociates from core TFIIH. A simplified, but general model of how various assembly and disassembly states of TFIIH can be invoked to explain different disease states is discussed. Accordingly, defects in specific enzymatic functions typically result in XP, dissociation of the CAK subunit from TFIIH is associated with XP/CS and a more generalized destabilization of TFIIH gives rise to TTD. While this classification provides a useful framework to understand how alterations in TFIIH correlate with disease states, it does not universally apply and relevant exception and alternative explanations are discussed.
    DNA Repair 03/2008; 7(2):339-44. DOI:10.1016/j.dnarep.2007.10.007 · 3.36 Impact Factor
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