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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human Cockayne Syndrome CS-B cells exposed to UV irradiation

ABSTRACT: Cockayne syndrome B (CSB) protein is a member of the SWI/SNF family and has DNA-dependent ATPase and ATP-dependent chromatin remodeling activities. The CSB protein is missing or altered in CS-B cells. CS-B cells are hypersensitive to UV light and defective in transcription-coupled DNA repair (TCR). TCR efficiently removes a variety of lesions from the transcribed strand of active genes. It has been shown that lesions specifically in the transcribed strand of active genes trigger the induction of apoptosis following UV irradiation. Several DNA damage signaling cascades, including the ATR/Chk1, p38 kinase, p53, and jun N-terminal kinase pathways are activated following UV irradiation. However, the role of TCR in cellular global transcriptional responses to UV irradiation remains to be elucidated. Using oligonucleotide microarray technology, we analyzed the time course of responses of CS-B cells (CS-B) and CS-B cells complemented with wild-type CSB cDNA (CS-B wt). Experiment Overall Design: In order to investigate the global transcriptional responses to UV damage in TCR-proficient or TCR-deficient cells, CS-B wt and CS-B cells were irradiated with 10 J/m2 of UV light and incubated for 2 or 12 hours. All experiments were performed in triplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Toshiro Matsuda

PROVIDER: E-GEOD-8939 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptional responses to UV irradiation in CS-B cells

Project description:Cockayne syndrome B (CSB) protein is a member of the SWI/SNF family and has DNA-dependent ATPase and ATP-dependent chromatin remodeling activities. The CSB protein is missing or altered in CS-B cells. CS-B cells are hypersensitive to UV light and defective in transcription-coupled DNA repair (TCR). TCR efficiently removes a variety of lesions from the transcribed strand of active genes. It has been shown that lesions specifically in the transcribed strand of active genes trigger the induction of apoptosis following UV irradiation. Several DNA damage signaling cascades, including the ATR/Chk1, p38 kinase, p53, and jun N-terminal kinase pathways are activated following UV irradiation. However, the role of TCR in cellular global transcriptional responses to UV irradiation remains to be elucidated. Using oligonucleotide microarray technology, we analyzed the time course of responses of CS-B cells (CS-B) and CS-B cells complemented with wild-type CSB cDNA (CS-B wt). Keywords: UV response, time course, disease state analysis

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Cockayne syndrome group A and ferrochelatase finely tune ribosomal gene transcription and its response to UV irradiation

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Project description:The response to DNA damage-stalled RNA polymerase II (RNAPIIo) involves the assembly of the transcription-coupled repair (TCR) complex on actively transcribed strands. The function of the TCR proteins CSB, CSA and UVSSA and the manner in which the core DNA repair complex, including transcription factor IIH (TFIIH), is recruited is largely unknown. Here, we define the assembly mechanism of the TCR complex in human isogenic knockout cells. We show that TCR is initiated by RNAPIIo-bound CSB, which recruits CSA through a newly identified CSA-interaction domain (CID). Once recruited, CSA facilitates the association of UVSSA with stalled RNAPIIo. Importantly, we find that UVSSA is the key factor that regulates the assembly of the TFIIH complex in a manner that is stabilized by CSB and CSA. We identify the UV-specific and independent interactors of UVSSA

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