Search for DNA repair factors binding to stalled-RNA polymerase II
| Project/Area Number |
17510043
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | National Kyushu Cancer Center Institute for Clinical Research (2006)
Osaka University (2005) |
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Principal Investigator |
KURAOKA Isao National Kyushu Cancer Center, Institute for Clinical Research, Principal Scientist, 研究室長 (60335396)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | DNA damage / DNA repair / RNA polymerase II / Transcription elongation / TFIIS / Translesion RNA synthesis |
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| Research Abstract |
Although genomic DNA contains genetic information that should be error free for the proper functioning of the cell, DNA is prone to deterioration and modifications due to environmental and endogenous damage. DNA lesion interferes with essential DNA-dependent processes such as DNA replication and transcription, and triggers mutations or cell death. All organisms have acquired various DNA repair systems to remove such lesions and to maintain genomic integrity. There are several major DNA repair pathways such as nucleotide excision repair (NER) operating primarily on bulky helix-distorting damage caused by environmental mutagens, and base excision repair (BER) for non-bulky and non-helix-distorting DNA modifications caused by endogenous and some chemical carcinogen-induced damage.
NER comprises two subpathways: global genome repair (GGR) and transcription-coupled repair (TCR). When RNA polymerase II (RNAP II) in the elongation phase encounters DNA damage that blocks transcription, TCR operates to counteract the interference with a immediate response. On the other hand, the DNA damage on the non-transcribed strand or in inactive regions is repaired by GGR. It is suggested that the TCR process is initiated by the blockage of transcription elongation by RNAPII at the DNA damage site. It has been reported that bulky and helix-distorting lesions blocked transcription elongation, and that these lesions are repaired by TCR.
We examined the effect of several types of oxidative DNA lesions (2-OH adenine, 8-oxo adenine, 8-oxo guanine, and thymine glycol) on transcription elongation in vitro, and found that RNAPII was stalled at these lesions. In addition, it was found that TFIIS (SII), a transcription elongation factor, enabled RNAPII to bypass 8-oxoG but not other types of oxidative DNA damage. We believe that SII-induced translesion RNA synthesis (TLRS) plays an important role in the toleration of oxidative DNA damage in the cell.
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Report
(3 results)
Research Products
(8 results)
