کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8320585 | 1539393 | 2015 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis
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کلمات کلیدی
p53PolδX-Ray Repair Cross-Complementing Protein 1DNA ligase IXRCC1APE1OGG1SSBMMRMMSBER8-oxoguanine DNA glycosylase - 8-اگزوگوئین دی ان ای گلیکوزیلازapurinic/apyrimidinic endonuclease 1 - apurinic / apyrimidinic endonuclease 1DNA polymerase β - DNA پلیمراز بNER - DOWNPolβ - PolbaROS - ROSSp1 - SP1nucleotide excision repair - تعمیر مجدد نوکلئوتیدیmismatch repair - تعمیر ناسازگاریbase excision repair - تعمیر پایه پایهCNS - دستگاه عصبی مرکزیabasic site - سایت نابجاNeurotoxicity - سمیت عصبیcentral nervous system - سیستم عصبی مرکزیsingle-strand break - شکستن تک رشتهmethyl methanesulfonate - متیل متان سولفوناتCadmium - کادمیمReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis Cadmium treatment suppresses DNA polymerase δ catalytic subunit gene expression by acting on the p53 and Sp1 regulatory axis](/preview/png/8320585.png)
چکیده انگلیسی
Cadmium (Cd) is a carcinogenic and neurotoxic environmental pollutant. Among the proposed mechanisms for Cd toxic effects, its ability to promote oxidative stress and to inhibit, in vitro, the activities of some Base Excision DNA Repair (BER) enzymes, such as hOGG1, XRCC1 and APE1, have been already established. However, the molecular mechanisms at the basis of these processes are largely unknown especially at sub-lethal doses of Cd and no information is available on the effect of Cd on the expression levels of BER enzymes. Here, we show that non-toxic treatment of neuronal cell lines, with pro-mitogenic doses of Cd, promotes a significant time- and dose-dependent down-regulation of DNA polymerase δ (POLD1) expression through a transcriptional mechanism with a modest effect on Polβ, XRCC1 and APE1. We further elucidated that the observed transcriptional repression on Polδ is acted by through competition by activated p53 on Sp1 at POLD1 promoter and by a squelching effect. We further proved the positive effect of Sp1 not only on POLD1 expression but also on Polβ, XRCC1 and APE1 expression, suggesting that Sp1 has pleiotropic effects on the whole BER pathway. Our results indicated that Cd-mediated impairment of BER pathway, besides acting on the enzymatic functions of some key proteins, is also exerted at the gene expression level of Polδ by acting on the p53-Sp1 regulatory axis. These data may explain not only the Cd-induced neurotoxic effects but also the potential carcinogenicity of this heavy metal.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 35, November 2015, Pages 90-105
Journal: DNA Repair - Volume 35, November 2015, Pages 90-105
نویسندگان
Giulia Antoniali, Federica Marcuzzi, Elena Casarano, Gianluca Tell,