کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8320782 | 1539406 | 2014 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Functional variants of human APE1 rescue the DNA repair defects of the yeast AP endonuclease/3â²-diesterase-deficient strain
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
8oxoGApurinic/apyrimidinic sitesSDSUDGDHU5-hydroxyuracilTHF5-OHUDTTMMSBLMPMSF5,6-dihydrouracil - 5،6-دی هیدروراآسیل8-oxoguanine - 8-اکسوگوینینUracil DNA glycosylase - DNA گلیکوزیلاز اوراسیلOxidative DNA damage - آسیب اکسیداتیو DNABleomycin - بلئومایسینTetrahydrofuran - تتراهیدروفورانDNA repair - ترمیم DNABase-excision repair - تعمیر پایه پایهmutations - جهش یا میوتیشنdithiothreitol - دیتیوتریتولAP sites - سایت های APsodium dodecyl sulphate - سدیم دودسیل سولفاتMethyl methane sulfonate - متیل متان سولفوناتYeast - مخمرH2O2 - هیدروژن پراکسیدpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Functional variants of human APE1 rescue the DNA repair defects of the yeast AP endonuclease/3â²-diesterase-deficient strain Functional variants of human APE1 rescue the DNA repair defects of the yeast AP endonuclease/3â²-diesterase-deficient strain](/preview/png/8320782.png)
چکیده انگلیسی
Human APE1 is an essential enzyme performing functions in DNA repair and transcription. It possesses four distinct repair activities acting on a variety of base and sugar derived DNA lesions. APE1 has seven cysteine residues and Cys65, and to a lesser extent Cys93 and Cys99, is uniquely involved in maintaining a subset of transcription factors in the reduced and active state. Four of the cysteines Cys93, 99, 208 and 310 of APE1 are located proximal to its active site residues Glu96, Asp210 and His309 involved in processing damaged DNA, raising the possibility that missense mutation of these cysteines could alter the enzyme DNA repair functions. An earlier report documented that serine substitution of the individual cysteine residues did not affect APE1 ability to cleave an abasic site oligonucleotide substrate in vitro, except for Cys99Ser, although any consequences of these variants in the repair of in vivo DNA lesions were not tested. Herein, we mutated all seven cysteines of APE1, either singly or in combination, to alanine and show that none of the resulting variants interfered with the enzyme DNA repair functions. Cross-specie complementation analysis reveals that these APE1 cysteine variants fully rescued the yeast DNA repair deficient strain YW778, lacking AP endonucleases and 3â²-diesterases, from toxicities caused by DNA damaging agents. Moreover, the elevated spontaneous mutations arising in strain YW778 from the lack of the DNA repair activities were completely suppressed by the APE1 cysteine variants. These findings suggest that the cysteine residues of APE1 are unlikely to play a role in the DNA repair functions of the enzyme in vivo. We also examine other APE1 missense mutations and provide the first evidence that the variant Asp308Ala with normal AP endonuclease, but devoid of 3ʹâ5ʹ exonuclease, displays hypersensitivity to the anticancer drug bleomycin, and not to other agents, suggesting that it has a defect in processing unique DNA lesions. Molecular modeling reveals that Asp308Ala cannot make proper contact with Mg2+ and may alter the enzyme ability to cleave or disassociate from specific DNA lesions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 22, October 2014, Pages 53-66
Journal: DNA Repair - Volume 22, October 2014, Pages 53-66
نویسندگان
Zhiqiang Wang, Emily Ayoub, Abdelghani Mazouzi, Inga Grin, Alexander A. Ishchenko, Jinjiang Fan, Xiaoming Yang, Taramatti Harihar, Murat Saparbaev, Dindial Ramotar,