کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10826159 | 1064727 | 2012 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
High-throughput screening for genes that prevent excess DNA replication in human cells and for molecules that inhibit them
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کلمات کلیدی
FACSHTSEDREndoreduplicationRNA interference - RNA تداخل کنندهSmall interfering RNA - RNA تداخل کوچکRNAi - RNA سرکوبگر،RNA مداخلهگر، RNA خاموش کنندهsiRNA - siRNAOff-target effects - اثرات غیر هدفEmi1 - امی 1endocycle - اندوسیکلرCancer - سرطانhigh throughput screening - غربالگری بالاfluorescence activated cell sorting - فلورسانس سلول فعال فعال سلولGeminin - کشتی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
High-throughput screening (HTS) provides a rapid and comprehensive approach to identifying compounds that target specific biological processes as well as genes that are essential to those processes. Here we describe a HTS assay for small molecules that induce either DNA re-replication or endoreduplication (i.e. excess DNA replication) selectively in cells derived from human cancers. Such molecules will be useful not only to investigate cell division and differentiation, but they may provide a novel approach to cancer chemotherapy. Since induction of DNA re-replication results in apoptosis, compounds that selectively induce DNA re-replication in cancer cells without doing so in normal cells could kill cancers in vivo without preventing normal cell proliferation. Furthermore, the same HTS assay can be adapted to screen siRNA molecules to identify genes whose products restrict genome duplication to once per cell division. Some of these genes might regulate the formation of terminally differentiated polyploid cells during normal human development, whereas others will prevent DNA re-replication during each cell division. Based on previous studies, we anticipate that one or more of the latter genes will prove to be essential for proliferation of cancer cells but not for normal cells, since many cancer cells are deficient in mechanisms that maintain genome stability.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Methods - Volume 57, Issue 2, June 2012, Pages 234-248
Journal: Methods - Volume 57, Issue 2, June 2012, Pages 234-248
نویسندگان
Chrissie Y. Lee, Ronald L. Johnson, Jennifer Wichterman-Kouznetsova, Rajarshi Guha, Marc Ferrer, Pinar Tuzmen, Scott E. Martin, Wenge Zhu, Melvin L. DePamphilis,