Genomic instability in incuded stem cells and regulation of P14ARF expression

Diplôme Thèse Genomic instability in incuded stem cells and regulation of P14ARF expression eng 2011-07-07 author Dereli Ayguel 647543 director Halazonetis Thanos 641033 10.13097/archive-ouverte/unige:17098 urn:nbn:ch:unige-170985 Sc. 4335 Part I. Genomic instability in induced stem cells - The ability to reprogram adult cells into stem cells has raised hopes for novel therapies. Expression of oncogenes leads to DNA replication stress and genomic instability, explaining the high frequency of p53 mutations in human cancers. We wondered whether stem cell reprogramming also leads to genomic instability. We examined stem cells induced by a variety of protocols. Comparative genomic hybridization analysis of stem cells revealed the presence of genomic deletions and amplifications, whose signature was suggestive of oncogene induced DNA replication stress. Part II. Regulation of p14ARF Expression - We examined the role of p14ARF in cancer. p14ARF is encoded by CDKN2A locus, which also encodes p16INK4A. By analysis of mRNA and protein levels, we found that E2F1 acts at the level of p14ARF mRNA. Identifying how p14ARF levels are regulated could be useful in therapeutic applications particularly in p53-defective cancers. Dewey 570 43 Département de biologie moléculaire 161 false 20f97944-8f5d-47f6-9ef4-95307879ba35 Thesis Public Aygul_Dereli.pdf 4328951 application/pdf openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Genomic instability in incuded stem cells and regulation of P14ARF expression				2011	782	548

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Dereli, Ayguel