التفاصيل البيبلوغرافية
| العنوان: |
The Role of Persistent Nicks at the Boundaries of Interphase Chromatin Loops and Their Possible Involvement in Pathological Gene Rearrangements ; Egyszál folytonossághiányok szerepe a kromatin hurkok kialakításában és patológiás génátrendeződésekben |
| المؤلفون: |
Székvölgyi, Lóránt |
| المساهمون: |
Szabó, Gábor, Elméleti orvostudományok doktori iskola, DE--OEC--Általános Orvostudományi Kar -- Biofizikai és Sejtbiológiai Intézet |
| سنة النشر: |
2006 |
| المجموعة: |
University of Debrecen Electronic Archive (DEA) / Debreceni Egyetem elektronikus Archívum |
| مصطلحات موضوعية: |
chromatin loop, kromatin hurok, loop-size chromatin fragmentation, hurok-méretű kromatin fragmentáció, translocation, transzlokáció, Mixed Lineage Leukemia (MLL) gene, Mixed Lineage Leukemia (MLL) gén, histone modification, hiszton modifikáció, ChIP-on-beads, Elméleti orvostudományok, Orvostudományok |
| الوصف: |
Although the higher-order structure of eukaryotic chromosomes has been the focus of considerable attention, little is known about the signals that mark the boundaries of interphase chromatin loops. The chromatin fragmentation phenomenon described herein seems particularly important because (a) it reflects regularities in the organization of higher order chromatin structure, (b) it appears to be interrelated with questions concerning genome instability, apoptosis and chemotherapy-associated gene rearrangements. Applying biophysical and molecular biological techniques (e.g. CLSM, LSC, flow cytometry, halo-FISH, FIGE-SSGE, ChIP), we have visualized the global disassembly of the chromatin of healthy, non-apoptotic human cells into particles apparently containing the DNA-loops, for the first time. Data we have obtained provide evidence for the existence of preformed single-strand discontinuities all over the entire genome, which appear to be arranged on the two DNA strands in an alternating, staggered fashion, positioned at loop-size intervals. The chemical nature of the DNA-termini have been characterized by in situ nick labeling, revealing uniform ends with 3’OH groups, tightly protected by structures sensitive to ribonucleolytic treatments. Our results suggest an association between the nicks present at the bases of chromatin loops and the nuclear matrix attached architectural hnRNA-network. To study the role of particular DNA regions in the observed phenomena, we extended our studies on the breakpoint cluster region (bcr) of the Mixed Lineage Leukemia (MLL) gene that is frequently rearranged in childhood and posttherapeutic leukemias. The sequence specificity of nick accumulation, the possible function of nick froming sequence motives as well as the role of topoisomerase II have been investigated by linear primer extension footprinting and chromatin immunoprecipitation (ChIP). The results demonstrate the involvement of the above enzyme in the generation / maintenance of nicks at non-random positions. As studied ... |
| نوع الوثيقة: |
other/unknown material |
| وصف الملف: |
105795 bytes; 147424 bytes; 26565 bytes; 4772146 bytes; 137216 bytes; 179200 bytes; 25600 bytes; 10348544 bytes; application/pdf; application/msword |
| اللغة: |
Hungarian
English |
| العلاقة: |
http://hdl.handle.net/2437/3289Test |
| الإتاحة: |
http://hdl.handle.net/2437/3289Test |
| رقم الانضمام: |
edsbas.E0A38D0 |
| قاعدة البيانات: |
BASE |
