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

Texas A&M University - Galveston, Galveston, Texas, United States
Cell (Impact Factor: 32.24). 07/2002; 109(7):823-34. DOI: 10.1016/S0092-8674(02)00795-X
Source: PubMed


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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    • "The rad2Δ mutant was highly sensitive to low dose UV radiation, and the survival of rad2E794A mutant decreased linearly with increasing UV radiation doses. In contrast, survival of the rad2C65Δ mutant clearly decreased in response to 20 J/m2 UV radiation; however, the dose-dependence of this decrease was significantly reduced at UV doses higher than 20 J/m2 (Fig. 1F) (Lee et al., 2002a). These findings indicate that the Rad2p C-terminal region has an unknown function in growth regulation following UV irradiation, and that the UV sensitivity and UV-induced cell growth retardation of the rad2C65Δ mutant are not simply the result of an NER defect. "
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    ABSTRACT: Mutations in the human XPG gene cause Cockayne syndrome (CS) and xeroderma pigmentosum (XP). Transcription defects have been suggested as the fundamental cause of CS; however, defining CS as a transcription syndrome is inconclusive. In particular, the function of XPG in transcription has not been clearly demonstrated. Here, we provide evidence for the involvement of RAD2, the Saccharomyces cerevisiae counterpart of XPG, in cell cycle regulation and efficient actin assembly following ultraviolet irradiation. RAD2 C-terminal deletion, which resembles the XPG mutation found in XPG/CS cells, caused cell growth arrest, the cell cycle stalling, a defective α-factor response, shortened lifespan, cell polarity defect, and misregulated actin-dynamics after DNA damage. Overexpression of the C-terminal 65 amino acids of Rad2p was sufficient to induce hyper-cell polarization. In addition, RAD2 genetically interacts with TPM1 during cell polarization. These results provide insights into the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly, which may be an underlying cause of XPG/CS.
    Full-text · Article · Dec 2013 · Biology Open
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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). "

    Full-text · Chapter · Oct 2011
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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). "

    Full-text · Chapter · Oct 2011
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