含有8-氧代-2'-脱氧鸟苷的端粒D-环是沃纳综合征和布卢姆综合征解旋酶的首选底物，并由端粒保护蛋白1（POT1）结合。
Telomeric D-loops containing 8-oxo-2'-deoxyguanosine are preferred substrates for Werner and Bloom syndrome helicases and are bound by POT1.
作者信息
Ghosh Avik, Rossi Marie L, Aulds Jason, Croteau Deborah, Bohr Vilhelm A
机构信息
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
出版信息
J Biol Chem. 2009 Nov 6;284(45):31074-84. doi: 10.1074/jbc.M109.027532. Epub 2009 Sep 4.
Abstract
8-Oxo-2'-deoxyguanosine (8-oxodG) is one of the most important oxidative DNA lesions, and G-rich telomeric DNA is especially susceptible to oxidative DNA damage. RecQ helicases WRN and BLM and telomere-binding protein POT1 are thought to play roles in telomere maintenance. This study examines the ability of WRN, BLM, and RecQ5 to unwind and POT1 to bind telomeric D-loops containing 8-oxodG. The results demonstrate that WRN and BLM preferentially unwind telomeric D-loops containing 8-oxodG and that POT1 binds with higher affinity to telomeric D-loops with 8-oxodG but shows no preference for telomeric single-stranded DNA with 8-oxodG. We speculate that telomeric D-loops with 8-oxodG may have a greater tendency to form G-quadruplex DNA structures than telomeric DNA lacking 8-oxodG.
摘要
8-氧代-2'-脱氧鸟苷（8-氧代dG）是最重要的氧化性DNA损伤之一，富含鸟嘌呤的端粒DNA尤其易受氧化性DNA损伤。RecQ解旋酶WRN和BLM以及端粒结合蛋白POT1被认为在端粒维持中发挥作用。本研究检测了WRN、BLM和RecQ5解开含有8-氧代dG的端粒D环的能力以及POT1结合此类端粒D环的能力。结果表明，WRN和BLM优先解开含有8-氧代dG的端粒D环，并且POT1对含有8-氧代dG的端粒D环具有更高的亲和力，但对含有8-氧代dG的端粒单链DNA没有偏好。我们推测，与缺乏8-氧代dG的端粒DNA相比，含有8-氧代dG的端粒D环可能更倾向于形成G-四链体DNA结构。
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本文引用的文献
1
Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance.从RecQ时代崛起：人类RecQ解旋酶在基因组维持中的作用。
Trends Biochem Sci. 2008 Dec;33(12):609-20. doi: 10.1016/j.tibs.2008.09.003. Epub 2008 Oct 14.
2
Mechanism and substrate specificity of telomeric protein POT1 stimulation of the Werner syndrome helicase.端粒蛋白POT1对沃纳综合征解旋酶的刺激机制及底物特异性
Nucleic Acids Res. 2008 Aug;36(13):4242-56. doi: 10.1093/nar/gkn385. Epub 2008 Jun 25.
3
Association of human DNA helicase RecQ5beta with RNA polymerase II and its possible role in transcription.人类DNA解旋酶RecQ5β与RNA聚合酶II的关联及其在转录中的可能作用。
Biochem J. 2008 Aug 1;413(3):505-16. doi: 10.1042/BJ20071392.
4
Telomere ResQue and preservation--roles for the Werner syndrome protein and other RecQ helicases.端粒修复与保护——沃纳综合征蛋白及其他RecQ解旋酶的作用
Mech Ageing Dev. 2008 Jan-Feb;129(1-2):79-90. doi: 10.1016/j.mad.2007.10.007. Epub 2007 Oct 30.
5
Guanines are a quartet's best friend: impact of base substitutions on the kinetics and stability of tetramolecular quadruplexes.鸟嘌呤是四联体的最佳“伙伴”：碱基替换对四分子四链体动力学和稳定性的影响
Nucleic Acids Res. 2007;35(9):3064-75. doi: 10.1093/nar/gkm111. Epub 2007 Apr 22.
6
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Cancer Res. 2006 Jul 15;66(14):6908-12. doi: 10.1158/0008-5472.CAN-06-1581.
7
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Angew Chem Int Ed Engl. 2006 Mar 27;45(14):2204-9. doi: 10.1002/anie.200502481.
8
The sacrificial role of easily oxidizable sites in the protection of DNA from damage.易氧化位点在保护DNA免受损伤中的牺牲作用。
Nucleic Acids Res. 2005 Sep 12;33(16):5133-8. doi: 10.1093/nar/gki801. Print 2005.
9
Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro.人类端粒保护蛋白1（POT1）可破坏端粒G-四链体结构，从而在体外使端粒酶得以延伸。
Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10864-9. doi: 10.1073/pnas.0504744102. Epub 2005 Jul 25.
10
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