The role of nuclear architecture in genomic instability and ageing

Abstract

Eukaryotes come in many shapes and sizes, yet one thing that they all seem to share is a decline in vitality and health over time--a process known as ageing. If there are conserved causes of ageing, they may be traced back to common biological structures that are inherently difficult to maintain throughout life. One such structure is chromatin, the DNA-protein complex that stabilizes the genome and dictates gene expression. Studies in the budding yeast Saccharomyces cerevisiae have pointed to chromatin reorganization as a main contributor to ageing in that species, which raises the possibility that similar processes underlie ageing in more complex organisms.

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

“…RB and P53 pathways are involved in biological effects induced by BRG1 silencing RB and P53 pathways are part of the core circuitry that controls cell cycle arrest, differentiation, apoptosis and/or senescence (Galderisi et al, 2006;Campisi and d'Adda di Fagagna, 2007;Oberdoerffer and Sinclair, 2007). Several reports showed that BRG1 operates through regulation of these key cellular pathways (Strobeck et al, 2000;Lee et al, 2002;Hendricks et al, 2004;Kang et al, 2004).…”

“…In fact, the H2AX activation and the upregulation in the expression BRG1, RB and P53 crosstalk Several reports suggested that BRG1 binds to and regulates the retinoblastoma protein and the tumor suppressor protein p53 (Strobeck et al, 2000;Lee et al, 2002;Hendricks et al, 2004;Kang et al, 2004). These are master genes that control cell cycle arrest, differentiation, apoptosis and/or senescence (Felsani et al, 2006;Galderisi et al, 2006;Campisi and d'Adda di Fagagna, 2007;Oberdoerffer and Sinclair, 2007). We tried to evaluate whether the biological effects of BRG1 silencing were related to RB-and P53-related pathways.…”

Higher-order Genome Organization in Human Disease

“…3). It has been suggested that the epigenetic alterations are largely triggered by DNA damage (reviewed in Oberdoerffer and Sinclair 2007). In this scenario, randomly occurring DNA damage leads to chromatin remodeling and to redistribution of chromatin modifiers within the genome with modifiers being recruited away from their normal sites so that they can engage in the repair of the DNA damage and others being recruited to newly available sites.…”

Epigenetic Alterations in Aging and Aging-Associated Diseases: Review

“…4 Yirminci yüzyılın ilk yarısında tanımlanan epigenetik, DNA nükleotid diziliminde değişiklik olmadan gen ifadesini kontrol eden ve aynı zamanda bir sonraki kuşaklara aktarılabilen değişik-liklerdir. 5,6 Epigenetik, embriyonik gelişim ve hücre farklılaşması gibi farklı biyolojik mekanizmalarda rol oynamaktadır. 7 Ayrıca, yapılan çalış-malar yaşlanma sırasında, genomik kararsızlığa neden olan ve gen ifadesini kontrol eden epigenetik değişimlerin önemini vurgulamaktadır.…”

“…6,44,54,55 miRNA'lar normal büyüme ve gelişme, yaş-lanma ve kanser olgularında genlerin düzenlenmesi için oldukça önemlidir. 16 Olgun miRNA 18-25 nük-leotid (nt) uzunluğunda olup ilk olarak saç tokası yapısına sahip primer-miRNA (pri-miRNA) molekülünden transkribe edilir ve translasyon sonrası gen susturulmasında rol alır.…”