Abstract
8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by post-replicative base excision repair (BER) initiated by adenine DNA glycosylase, MYH, creating an apurinic (AP) site. The subsequent mechanism ensuring a dC:8-oxo-dG pair, a substrate for 8-oxo-guanine DNA glycosylase (OGG1), remains to be elucidated. At the nucleotide insertion step, none of the mammalian DNA polymerases examined exclusively inserted dC opposite 8-oxo-dG that was located in a gap. AP endonuclease 1, which possesses 3′→5′ exonuclease activity and potentially serves as a proofreader, did not discriminate dA from dC that was located opposite 8-oxo-dG. However, human DNA ligases I and III joined 3′-dA terminus much more efficiently than 3AC terminus when paired to 8-oxo-dG. In reconstituted short-patch BER, repair products contained only dA opposite 8-oxo-dG. These results indicate that human DNA ligases discriminate dC from dA and that MYH-initiated short-patch BER is futile and hence this BER must proceed to long-patch repair, even if it is initiated as short-patch repair, through strand displacement synthesis from the ligation-resistant dC terminus to generate the OGG1 substrate, dC:8-oxo-dG pair.
| Original language | English |
|---|---|
| Pages (from-to) | 5928-5934 |
| Number of pages | 7 |
| Journal | Nucleic acids research |
| Volume | 32 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Dec 22 2004 |
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All Science Journal Classification (ASJC) codes
- Genetics
Cite this
Futile short-patch DNA base excision repair of adenine : 8-oxoguanine mispair. / Hashimoto, Keiji; Tominaga, Yohei; Nakabeppu, Yusaku; Moriya, Masaaki.
In: Nucleic acids research, Vol. 32, No. 19, 22.12.2004, p. 5928-5934.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Futile short-patch DNA base excision repair of adenine
T2 - 8-oxoguanine mispair
AU - Hashimoto, Keiji
AU - Tominaga, Yohei
AU - Nakabeppu, Yusaku
AU - Moriya, Masaaki
PY - 2004/12/22
Y1 - 2004/12/22
N2 - 8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by post-replicative base excision repair (BER) initiated by adenine DNA glycosylase, MYH, creating an apurinic (AP) site. The subsequent mechanism ensuring a dC:8-oxo-dG pair, a substrate for 8-oxo-guanine DNA glycosylase (OGG1), remains to be elucidated. At the nucleotide insertion step, none of the mammalian DNA polymerases examined exclusively inserted dC opposite 8-oxo-dG that was located in a gap. AP endonuclease 1, which possesses 3′→5′ exonuclease activity and potentially serves as a proofreader, did not discriminate dA from dC that was located opposite 8-oxo-dG. However, human DNA ligases I and III joined 3′-dA terminus much more efficiently than 3AC terminus when paired to 8-oxo-dG. In reconstituted short-patch BER, repair products contained only dA opposite 8-oxo-dG. These results indicate that human DNA ligases discriminate dC from dA and that MYH-initiated short-patch BER is futile and hence this BER must proceed to long-patch repair, even if it is initiated as short-patch repair, through strand displacement synthesis from the ligation-resistant dC terminus to generate the OGG1 substrate, dC:8-oxo-dG pair.
AB - 8-Oxo-7, 8-dihydrodeoxyguanosine (8-oxo-dG), one of the representative oxidative DNA lesions, frequently mispairs with the incoming dAMP during mammalian DNA replication. Mispaired dA is removed by post-replicative base excision repair (BER) initiated by adenine DNA glycosylase, MYH, creating an apurinic (AP) site. The subsequent mechanism ensuring a dC:8-oxo-dG pair, a substrate for 8-oxo-guanine DNA glycosylase (OGG1), remains to be elucidated. At the nucleotide insertion step, none of the mammalian DNA polymerases examined exclusively inserted dC opposite 8-oxo-dG that was located in a gap. AP endonuclease 1, which possesses 3′→5′ exonuclease activity and potentially serves as a proofreader, did not discriminate dA from dC that was located opposite 8-oxo-dG. However, human DNA ligases I and III joined 3′-dA terminus much more efficiently than 3AC terminus when paired to 8-oxo-dG. In reconstituted short-patch BER, repair products contained only dA opposite 8-oxo-dG. These results indicate that human DNA ligases discriminate dC from dA and that MYH-initiated short-patch BER is futile and hence this BER must proceed to long-patch repair, even if it is initiated as short-patch repair, through strand displacement synthesis from the ligation-resistant dC terminus to generate the OGG1 substrate, dC:8-oxo-dG pair.
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UR - http://www.scopus.com/inward/citedby.url?scp=10244255214&partnerID=8YFLogxK
U2 - 10.1093/nar/gkh909
DO - 10.1093/nar/gkh909
M3 - Article
C2 - 15531653
AN - SCOPUS:10244255214
VL - 32
SP - 5928
EP - 5934
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 19
ER -