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[Damage to the genome, p53 and cell polyploidization in ontogeny]
1Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
Abstract:
The protein p53 is a universal tumor suppressor in humans and negative regulator of cell proliferation, which is induced in cells in response to the damage of DNA and controls arrest of the cell cycle at specific checkpoints. A recently discovered function of gene p53 is the maintenance of the diploid state of the genome and a block of the formation of the population of cycling polyploids. This review examines models of disturbed control of the cell cycle due to loss, inactivation, or hyperexpression of gene p53 or its effector gene p21 in transgenic animals, i.e., homozygous mutant mice (p53-/-), (ERCC-1-/-), as well as in genetically defective cell lines in vitro. We discuss mechanisms responsible for the transition from the diploid to the polyploid state owing to the disturbed control of cell cycle by p53 and arising during the ontogenetic polyploidization of cells in normal animals.
Insights
The tumor suppressor protein p53 normally prevents polyploidy by regulating cell cycle checkpoints. Its loss or inactivation can lead to genome instability and polyploidization, contributing to cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Context:
- The protein p53 is a crucial tumor suppressor and cell cycle regulator in humans.
- p53 responds to DNA damage by arresting the cell cycle.
- Recent findings highlight p53's role in maintaining genomic diploidy and preventing polyploidization.
Purpose:
- To review models of cell cycle control disruption.
- To examine the consequences of p53 or p21 gene alterations.
- To discuss the mechanisms of diploid-to-polyploid transition.
Summary:
- This review analyzes cell cycle dysregulation in transgenic animals (p53-/- mice) and cell lines with defective p53 or its effector p21.
- It explores how loss, inactivation, or hyperexpression of p53/p21 impacts cell cycle control and genome stability.
- Mechanisms underlying the transition from diploid to polyploid states due to impaired p53 function are discussed.
Impact:
- Provides insights into the role of p53 in preventing genomic instability and polyploidy.
- Contributes to understanding cancer development mechanisms related to cell cycle control.
- Informs research on therapeutic strategies targeting p53 in cancer treatment.