کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10824045 | 1061965 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Proliferation-dependent expression of nuclear uracil-DNA glycosylase is mediated in part by E2F-4
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
There are two isoforms of the prototypical human uracil-DNA glycosylase: one mitochondrial (UDG1) and one nuclear (UDG1A). Results presented here reveal a novel genetic organization of UDG1. Specifically, the UDG1 5â² UTR is composed of two non-coding exons and the promoter region is located much farther upstream than previously recognized. We also examine the proliferation-dependent expression of UDG1A and demonstrate that the protein disappears rapidly as cells transit from the cell cycle into G0. Ribonuclease protection assays reveal that UDG1A mRNA levels are greatly reduced during G0 as well. To begin to characterize the mechanisms contributing to this regulation, we identified two overlapping candidate E2F binding sites (denoted A and B) in the UDG1A 5â² UTR. EMSA analysis of this region shows a unique protein complex present only in extracts derived from G0 cells. In vitro studies using purified E2F-4 and mutant competitors demonstrate that binding occurs in a proliferation-dependent manner exclusively to E2F site A. Two approaches were then used to assess the in vivo role of the candidate E2F sites. First, chromatin immunoprecipitation (ChIP) analysis demonstrates that E2F-4 binds to the UDG1A 5â² UTR exclusively in G0 cells. Secondly, using transient transfection analysis, we show that mutating these sites abolishes the proliferation-dependent response of UDG1A.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 4, Issue 2, 3 February 2005, Pages 183-190
Journal: DNA Repair - Volume 4, Issue 2, 3 February 2005, Pages 183-190
نویسندگان
Susan Muller-Weeks, Richard J. Balzer, Raina Anderson, Sal Caradonna,