Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/33341
Title: NBS1 Deficiency promotes genome instability by affecting DNA damage signaling pathway and impairing telomere integrity
Authors: HOU YANYAN
Keywords: NBS1, ATM, DNA damage, telomere, TRF2, genome instability
Issue Date: 10-Jan-2012
Source: HOU YANYAN (2012-01-10). NBS1 Deficiency promotes genome instability by affecting DNA damage signaling pathway and impairing telomere integrity. ScholarBank@NUS Repository.
Abstract: Studies revealed that NBS1 plays important roles in maintaining genome stability, but the underlying mechanism is controversial and elusive. Our study using clinical samples showed that NBS1 was involved in ATM/ATR-dependent pathways. NBS1 deficiency severely affected the phosphorylation of ATM/ATR as well as their downstream targets. The inefficiency in activating ATM/ATR-dependent pathways led to multiple defects in cellular responses towards DNA damage, such as inefficiency in inhibiting DNA synthesis and resistance to DNA-damaging agent. Accelerated telomere shortening was also observed in NBS fibroblasts, consistent with an earlier onset of cellular replicative senescence in vitro. This abnormality may be due to the shelterin protein TRF2 which was found upregulated in NBS fibroblasts. Prevalent telomeric fusions and cellular aneuploidy were also observed in NBS fibroblasts. Collectively, our study suggests a possible mechanism that NBS1 deficiency simultaneously affects ATM/ATR-dependent pathways and TRF2-regulated telomere maintenance, which synergistically lead to genomic abnormalities.
URI: http://scholarbank.nus.edu.sg/handle/10635/33341
Appears in Collections:Master's Theses (Open)

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