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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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Developmental Acquisition of p53 Functions
Sushil K Jaiswal1,2, Sonam Raj3, Melvin L DePamphilis1
1National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Genes
|November 27, 2021
Summary
The p53 transcription factor is not essential for mammalian development, despite its role in DNA repair. p53 influences embryonic stem cell genomic stability and differentiation, but not pluripotency or all apoptosis pathways.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- The p53 transcription factor, known as "the guardian of the genome", is crucial for DNA repair and preventing cancer.
- Its role in mammalian development has been debated, with conflicting conclusions regarding p53-dependent developmental events.
- Pluripotent stem cells are vital models for mammalian development and have applications in regenerative medicine and disease research.
Purpose of the Study:
- To reconcile conflicting data on the role of p53 in mammalian development.
- To clarify the specific functions of p53 in embryonic stem cells (ESCs) and embryonic fibroblasts.
- To determine the necessity of p53 for pluripotency, genomic stability, and cell fate decisions during development.
Main Methods:
- Literature review and data reconciliation.
- Analysis of p53-dependent transcription during mouse embryogenesis.
- Investigation of p53's role in ESCs and embryonic fibroblasts concerning DNA damage response, cell cycle arrest, apoptosis, senescence, and differentiation.
Main Results:
- p53-dependent transcription is first detected in late mouse blastocysts, with p53 activity becoming potentially lethal during gastrulation.
- p53 is not required for pluripotency in ESCs but contributes to their genomic stability and differentiation.
- While p53 can accelerate apoptosis in ESCs under certain conditions, cell cycle arrest and the extent of apoptosis are p53-independent.
- In embryonic fibroblasts, p53 induces cell cycle arrest for DNA repair and promotes senescence to prevent proliferation of damaged cells.
Conclusions:
- p53 is not essential for mammalian development but plays critical roles in specific cellular processes.
- p53's functions in ESCs involve maintaining genomic stability and guiding differentiation, rather than regulating pluripotency.
- The p53 pathway's involvement in DNA damage response varies between cell types and developmental stages, impacting apoptosis and cell cycle control differently.
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