TY - JOUR
T1 - Translocation of cockayne syndrome group A protein to the nuclear matrix
T2 - Possible relevance to transcription-coupled DNA repair
AU - Kamiuchi, Shinya
AU - Saijo, Masafumi
AU - Citterio, Elisabetta
AU - De Jager, Martijn
AU - Hoeijmakers, Jan H.J.
AU - Tanaka, Kiyoji
PY - 2002/1/8
Y1 - 2002/1/8
N2 - Transcription-coupled repair (TCR) efficiently removes a variety of lesions from the transcribed strand of active genes. By allowing rapid resumption of RNA synthesis, the process is of major importance for cellular resistance to transcription-blocking genotoxic damage. Mutations in the Cockayne syndrome group A or B (CSA or CSB) gene result in defective TCR. However, the exact mechanism of TCR in mammalian cells remains to be elucidated. We found that CSA protein is rapidly translocated to the nuclear matrix after UV irradiation. The translocation of CSA was independent of Xeroderma pigmentosum group C, which is specific to the global genome repair subpathway of nucleotide excision repair (NER) and of the core NER factor Xeroderma pigmentosum group A but required the CSB protein, in UV-irradiated cells, CSA protein colocalized with the hyperphosphorylated form of RNA polymerase II, engaged in transcription elongation. The translocation of CSA was also induced by treatment of the cells with cisplatin or hydrogen peroxide, both of which produce damage that is subjected to TCR but not induced by treatment with dimethyl sulfate, which produces damage that is not subjected to TCR. The hydrogen peroxide-induced translocation of CSA was also CSB dependent. These findings establish a link between TCR and the nuclear matrix mediated by CSA.
AB - Transcription-coupled repair (TCR) efficiently removes a variety of lesions from the transcribed strand of active genes. By allowing rapid resumption of RNA synthesis, the process is of major importance for cellular resistance to transcription-blocking genotoxic damage. Mutations in the Cockayne syndrome group A or B (CSA or CSB) gene result in defective TCR. However, the exact mechanism of TCR in mammalian cells remains to be elucidated. We found that CSA protein is rapidly translocated to the nuclear matrix after UV irradiation. The translocation of CSA was independent of Xeroderma pigmentosum group C, which is specific to the global genome repair subpathway of nucleotide excision repair (NER) and of the core NER factor Xeroderma pigmentosum group A but required the CSB protein, in UV-irradiated cells, CSA protein colocalized with the hyperphosphorylated form of RNA polymerase II, engaged in transcription elongation. The translocation of CSA was also induced by treatment of the cells with cisplatin or hydrogen peroxide, both of which produce damage that is subjected to TCR but not induced by treatment with dimethyl sulfate, which produces damage that is not subjected to TCR. The hydrogen peroxide-induced translocation of CSA was also CSB dependent. These findings establish a link between TCR and the nuclear matrix mediated by CSA.
UR - http://www.scopus.com/inward/record.url?scp=0037039443&partnerID=8YFLogxK
U2 - 10.1073/pnas.012473199
DO - 10.1073/pnas.012473199
M3 - Article
C2 - 11782547
AN - SCOPUS:0037039443
SN - 0027-8424
VL - 99
SP - 201
EP - 206
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -