کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1927220 | 1536507 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Presence of the anti-leukemic nucleotide analog, 2-chloro-2â²-deoxyadenosine-5â²-monophosphate, in a promoter sequence alters DNA binding of TATA-binding protein (TBP)
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کلمات کلیدی
RNA polymerase II - آرانای پلیمراز II Promoter sequence - توالی تبلیغ کنندهCancer drug - داروی سرطانیProtein conformation - سازگاری پروتئینDNA minor groove - شیار DNA جزئیTranscription factors - عوامل رونویسیhairy cell leukemia - لوسمی سلول مویTATA-binding protein - پروتئین متصل به TATACladribine - کلدریبیون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
2-Chlorodeoxyadenosine (CldAdo, Cladribine), a nucleoside analog used in the treatment of hairy cell leukemia, is phosphorylated and incorporated into DNA, but is not an absolute chain terminator. We hypothesized that the presence of a chlorine molecule projecting into the DNA minor groove would affect DNA:protein-binding interactions. Here, we investigated recognition of and binding to double-stranded CldAMP-substituted TATA promoter sequences by human TATA-binding protein (TBP) using mobility shift assays. Depending on the site, CldAMP in place of dAMP within a TATA sequence decreased in vitro TBP binding by â¼30% to 55% compared to control sites. When bound to a CldAMP-substituted TATA box, however, the TBP complex was more resistant to polyanions, suggesting enhanced stability. Limited exposure of the TBP:DNA complex to proteases indicated that TBP conformation was altered on CldAMP-substituted DNA compared to control. Further, binding of transcription factor IIB to TBP was diminished on analog-containing TATA sequences. These results suggest normal TBP-binding interactions-specifically recognition, stability, and conformation-are disrupted by CldAMP insertion into eukaryotic promoter sequences.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 459, Issue 2, 15 March 2007, Pages 223-232
Journal: Archives of Biochemistry and Biophysics - Volume 459, Issue 2, 15 March 2007, Pages 223-232
نویسندگان
William R. Hartman, D. Eric Walters, Patricia Hentosh,