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与XRCC1缺陷相关的簇状损伤位点内无碱基位点/单链断裂损伤的碱基切除修复过程。

Base excision repair processing of abasic site/single-strand break lesions within clustered damage sites associated with XRCC1 deficiency.

作者信息

Mourgues Sophie, Lomax Martine E, O'Neill Peter

机构信息

Medical Research Council, Radiation and Genome Stability Unit, Harwell, Didcot, Oxfordshire OX11 ORD, UK.

出版信息

Nucleic Acids Res. 2007;35(22):7676-87. doi: 10.1093/nar/gkm947. Epub 2007 Nov 3.

DOI:10.1093/nar/gkm947
PMID:17982170
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2190709/
Abstract

Ionizing radiation induces clustered DNA damage, which presents a challenge to the cellular repair machinery. The repair efficiency of a single-strand break (SSB) is approximately 4x less than that for repair of an abasic (AP) site when in a bistranded cluster containing 8-oxoG. To explore whether this difference in repair efficiency involves XRCC1 or other BER proteins, synthetic oligonucleotides containing either an AP site or HAP1-induced SSB (HAP1-SSB) 1 or 5 bp 5' or 3' to 8-oxoG on the opposite strand were synthesized and the repair investigated using either nuclear extracts from hamster cells proficient (AA8) or deficient (EM7) in XRCC1 or purified BER proteins. XRCC1 is important for efficient processing of an AP site in clustered damage containing 8-oxoG but does not affect the already low repair efficiency of a SSB. Ligase I partly compensates for the absence of the XRCC1/ligaseIII during short-patch BER of an AP site when in a cluster but only weakly if at all for a HAP1-SSB. The major difference between the repair of an AP site and a HAP1-SSB when in a 8-oxoG containing cluster is the greater efficiency of short-patch BER with the AP site compared with that for a HAP1-SSB.

摘要

电离辐射会诱发成簇的DNA损伤，这对细胞修复机制构成了挑战。当处于含有8-氧代鸟嘌呤（8-oxoG）的双链簇中时，单链断裂（SSB）的修复效率比无碱基（AP）位点的修复效率低约4倍。为了探究这种修复效率的差异是否涉及XRCC1或其他碱基切除修复（BER）蛋白，合成了在相反链上与8-oxoG在5'或3'端相差1或5个碱基对处含有AP位点或HAP1诱导的SSB（HAP1-SSB）的合成寡核苷酸，并使用来自XRCC1功能正常（AA8）或缺陷（EM7）的仓鼠细胞的核提取物或纯化的BER蛋白来研究修复情况。XRCC1对于高效处理含有8-oxoG的成簇损伤中的AP位点很重要，但不影响已经很低的SSB修复效率。在成簇的AP位点短片段BER过程中，连接酶I部分补偿了XRCC1/连接酶III的缺失，但对于HAP1-SSB，即使有补偿作用也很微弱。当处于含有8-oxoG的簇中时，AP位点和HAP1-SSB修复之间的主要差异在于，与HAP1-SSB相比，AP位点的短片段BER效率更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/ea09b6764b01/gkm947f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/15778042ccd8/gkm947f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/97b46b9f9c73/gkm947f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/a054a36931fc/gkm947f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/6e3d1c03c7f0/gkm947f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/5ec8110534b8/gkm947f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/784f6d033218/gkm947f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/ea09b6764b01/gkm947f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/15778042ccd8/gkm947f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/97b46b9f9c73/gkm947f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/a054a36931fc/gkm947f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/6e3d1c03c7f0/gkm947f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/5ec8110534b8/gkm947f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/784f6d033218/gkm947f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22e5/2190709/ea09b6764b01/gkm947f7.jpg

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2
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3
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4
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Cells. 2021 Nov 20;10(11):3254. doi: 10.3390/cells10113254.
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6
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J Radiat Res. 2019 Jan 1;60(1):69-79. doi: 10.1093/jrr/rry096.
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9
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