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Expression data from BJ-hTERT cells expressing shRNA control vector or shRNA against p53.

ABSTRACT: p53 is a major tumor suppressor gene that is frequently inactivated in human cancers. One prominent suppressive function of p53 is executing cell cycle arrest, senescence and apoptosis upon stress. Importantly, p53 loss is a prerequisite for cancer development, as is evident in Li-Fraumeni patients and p53 knockout mice. Here we investigated the effect of p53-loss, without induction of additional stress, on DNA replication and genomic instability. We revealed that p53 deficiency leads to enhanced proliferation without upregulating essential pathways requited to support normal DNA replication. This uncoordinated S-phase entry leads to replication-induced genomic instability. Interestingly, DNA replication analyses revealed a novel and non-classical form of replication stress induced by p53-loss, characterized by reduced fork rate progression without the compensation of dormant origin activation. Altogether, the results reveal a non-canonical tumor suppressive role of p53 in regulating DNA replication which safeguards genomic stability, underlying cancer predisposition induced by p53-loss. In order to understand the molecular basis for shp53 non-classical form of replication stress and replication-induced genomic instability, we performed unbiased whole transcriptome analysis of BJ-hTERT control cells in comparison to BJ-hTERT cells expressing shRNA against p53. Our results suggest that shp53 cells fail to upregulate essential pathways required for normal DNA replication.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93046 | GEO | 2025/06/01

REPOSITORIES: GEO

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