کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10905859 | 1086770 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation
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کلمات کلیدی
BFBHSRMARDMSAnaphase bridgedouble minutesGenomic instability - بی ثباتی ژنوم Gene amplification - تقویت ژنbreakage-fusion-bridge - شکستن فیوژن پلfluorescence in situ hybridization - فلورسانس در هیبریداسیون در محلFish - ماهیmatrix attachment region - منطقه دلبستگی ماتریکسhomogeneously staining region - همگن رنگ آمیزی منطقه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Amplified genes are frequently localized on extrachromosomal double minutes (DMs) or in chromosomal homogenously staining regions (HSRs). We previously showed that a plasmid bearing a mammalian replication initiation region could efficiently generate DMs and HSRs after transfection into human tumor cell lines. The Breakage-Fusion-Bridge (BFB) cycle model, a classical model that explains how HSRs form, could also be used to explain how the transfected plasmids generate HSRs. The BFB cycle model involves anaphase bridge formation due to the presence of dicentric chromosomes, followed by the breakage of the bridge. In this study, we used our plasmid-based model system to analyze how anaphase bridges break during mitosis. Dual-color fluorescence in situ hybridization analyses revealed that anaphase bridges were most frequently severed in their middle irrespective of their lengths, which suggests that a structurally fragile site exists in the middle of the anaphase bridge. Breakage of the chromosomal bridges occurred prior to nuclear membrane reformation and the completion of cytokinesis, which indicates that mechanical tension rather than cytokinesis is primarily responsible for severing anaphase bridges. Time-lapse observation of living cells revealed that the bridges rapidly shrink after being severed. If HSR length was extended too far, the bridge could no longer be resolved and became tangled depending on the tension. The unbroken bridge appeared to inhibit the completion of cytokinesis. These observations strongly suggest that anaphase bridges are highly elastic and that the length of the spindle axis determines the maximal HSR length.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 302, Issue 2, 15 January 2005, Pages 233-243
Journal: Experimental Cell Research - Volume 302, Issue 2, 15 January 2005, Pages 233-243
نویسندگان
Noriaki Shimizu, Kenta Shingaki, Yukiko Kaneko-Sasaguri, Toshihiko Hashizume, Teru Kanda,