RNA polymerase II bypasses 8-oxoguanine in the presence of transcription elongation factor TFIIS.
The blockage of transcription elongation by RNA polymerase II (RNAPII) at DNA lesions on the transcribed strand is a serious challenge to accurate transcription. Transcription-coupled DNA repair (TCR), which is assumed to be initiated by the blockage of transcription, rapidly removes lesions on the transcribed strand of expressed genes and allows the resumption of transcription. Although helix-distorting bulky damage such as a cyclobutane pyrimidine dimer is known to block transcription elongation and to be repaired by TCR, it is not clear whether oxidative DNA lesions are repaired by TCR. First, we examined whether transcription elongation by RNAPII is stalled at sites of 2-hydroxyadenine (2-OH-A), 8-oxoadenine (8-oxoA), 8-oxoguanine (8-oxoG), or thymine glycol (Tg) on the transcribed strand. Our results indicate that RNAPII incorporated nucleotides opposite the lesions and then stalled. In addition, we found that transcription elongation factor TFIIS (SII) enabled RNAPII to bypass 8-oxoG but not the other types of damage, while transcription initiation and elongation factor TFIIF did not bypass 8-oxoG. These results suggest that SII is important for preventing cellular death due to oxidative DNA damage, assisting RNAPII to bypass 8-oxoG.
Kuraoka
Isao
I
Laboratories for Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan. ikuraoka@nk-cc.go.jp <ikuraoka@nk-cc.go.jp>
Suzuki
Kyoko
K
Ito
Shinsuke
S
Hayashida
Mika
M
Kwei
Joan Seah Mei
JS
Ikegami
Takahisa
T
Handa
Hiroshi
H
Nakabeppu
Yusaku
Y
Tanaka
Kiyoji
K
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008956:Models, Chemical; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D013941:Thymine / Q000031:analogs & derivatives / Q000494:pharmacology; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; C002992:8-hydroxyadenine; C029389:thymine glycol; C024829:8-hydroxyguanine; D006147:Guanine; C008183:isoguanine; D012319:RNA Polymerase II; D000225:Adenine; D013941:Thymine; D010100:Oxygen