Details

Autor(en) / Beteiligte

• Cavga, Ayse Derya
• Tardu, Mehmet
• Korkmaz, Tuba
• Keskin, Ozlem
• Ozturk, Nuri
• Gursoy, Attila
• Kavakli, Ibrahim Halil

Titel

Cryptochrome deletion in p53 mutant mice enhances apoptotic and anti-tumorigenic responses to UV damage at the transcriptome level

Ist Teil von

• Functional & integrative genomics, 2019-09, Vol.19 (5), p.729-742

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2019

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Previous studies have demonstrated that deletion of cryptochrome ( Cry ) genes protects p53 −/− mutant mice from the early onset of cancer and extends their median life-span by about 1.5-fold. Subsequent in vitro studies had revealed that deletion of Cry s enhances apoptosis in response to UV damage through activation of p73 and inactivation of GSK3β. However, it was not known at the transcriptome-wide level how deletion of Cry s delays the onset of cancer in p53 −/− mutant mice. In this study, the RNA-seq approach was taken to uncover the differentially expressed genes (DEGs) and pathways following UV-induced DNA damage in p53 −/− and p53 −/− Cry1 −/− Cry2 −/− mouse skin fibroblasts. Gene set enrichment analysis with the DEGs demonstrated enrichment in immune surveillance-associated genes regulated by IFN-γ and genes involved in TNF α signaling via NF-κB. Furthermore, protein network analysis enabled identification of DEGs p21 , Sirt1 , and Jun as key players, along with their interacting partners. It was also observed that the DEGs contained a high ratio of non-coding transcripts. Collectively, the present study suggests new genes in NF-κB regulation and IFN-γ response, as well as non-coding RNAs, may contribute to delaying the onset of cancer in p53 −/− Cry1 −/− Cry2 −/− mice and increasing the life-span of these animals compared to p53 −/− mice.