کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10823354 | 1061826 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
DNA modifications repaired by base excision repair are epigenetic
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کلمات کلیدی
HMCoxoguanine glycosylaseAPEX1cAMP response element modulatorOGG1CREBBERRNSCRETHF5-Methylcytosine - 5-متیل سیتوزین8-oxo-7,8-dihydroguanine - 8-اکسو-7،8-دی هیدروگوانینROS - ROSAbasic - آبادیEpigenetics - اپی ژنتیکTetrahydrofuran - تتراهیدروفورانDNA–protein interaction - تعامل DNA-پروتئینDNA base excision repair - تعمیر DNA استخراج پایه DNAbase excision repair - تعمیر پایه پایهcAMP response element - عنصر پاسخ cAMPTranscription factors - عوامل رونویسیactivation induced deaminase - فعال شدن دامیناز القا شدهHmu - هومhydroxymethylcytosine - هیدروکسی متیل سیتوزینCREm - کرم رنگChromatin - کروماتینAID - کمکreactive nitrogen species - گونه های واکنش پذیر نیتروژنReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
CREB controls â¼25% of the mammalian transcriptome. Small changes in binding to its consensus (CRE) sequence are likely to be amplified many fold in initiating transcription. Here we show that DNA lesions repaired by the base excision repair (BER) pathway modulate CREB binding to CRE. We generated Kd values by electrophoretic mobility shift assays using purified human CREB and a 39-mer double-stranded oligonucleotide containing modified or wild-type CRE. CRE contains two guanine residues per strand, one in a CpG islet. Alterations in CRE resulted in positive or negative changes in Kd over two orders of magnitude depending on location and modification. Cytosine methylation or oxidation of both guanines greatly diminished binding; a G/U mispair in the CpG context enhanced binding. Intermediates in the BER pathway at one G residue or the other resulted in reduced binding, depending on the specific location, while there was no change in binding when the single G residue outside of the CpG islet was oxidized. CREB recruits other partners after dimers form on DNA. Only UpG increased DNA.CREB dimer formation. Since oxidation is ongoing and conversion of cytosine to uracil occurs spontaneously or at specific times during differentiation and development, we propose that BER substrates are epigenetic and modulate transcription factor recognition/binding.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 12, Issue 12, December 2013, Pages 1152-1158
Journal: DNA Repair - Volume 12, Issue 12, December 2013, Pages 1152-1158
نویسندگان
Stephen P.G. Moore, Kimberly J. Toomire, Phyllis R. Strauss,