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Review

Revisiting the Function of p21CDKN1A in DNA Repair: The Influence of Protein Interactions and Stability

1
Istituto di Genetica Molecolare “Luigi Luca Cavalli-Sforza”, Consiglio Nazionale delle Ricerche (CNR), Via Abbiategrasso 207, 27100 Pavia, Italy
2
Dipartimento di Biologia e Biotecnologie, Università di Pavia, Via Ferrata 9, 27100 Pavia, Italy
3
Dipartimento di Medicina Molecolare, Università di Pavia, Via Ferrata 9, 27100 Pavia, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Janusz Blasiak
Int. J. Mol. Sci. 2022, 23(13), 7058; https://doi.org/10.3390/ijms23137058
Received: 13 May 2022 / Revised: 22 June 2022 / Accepted: 23 June 2022 / Published: 24 June 2022
The p21CDKN1A protein is an important player in the maintenance of genome stability through its function as a cyclin-dependent kinase inhibitor, leading to cell-cycle arrest after genotoxic damage. In the DNA damage response, p21 interacts with specific proteins to integrate cell-cycle arrest with processes such as transcription, apoptosis, DNA repair, and cell motility. By associating with Proliferating Cell Nuclear Antigen (PCNA), the master of DNA replication, p21 is able to inhibit DNA synthesis. However, to avoid conflicts with this process, p21 protein levels are finely regulated by pathways of proteasomal degradation during the S phase, and in all the phases of the cell cycle, after DNA damage. Several lines of evidence have indicated that p21 is required for the efficient repair of different types of genotoxic lesions and, more recently, that p21 regulates DNA replication fork speed. Therefore, whether p21 is an inhibitor, or rather a regulator, of DNA replication and repair needs to be re-evaluated in light of these findings. In this review, we will discuss the lines of evidence describing how p21 is involved in DNA repair and will focus on the influence of protein interactions and p21 stability on the efficiency of DNA repair mechanisms. View Full-Text
Keywords: p21CDKN1A; DNA repair; DNA damage response; PCNA; protein degradation p21CDKN1A; DNA repair; DNA damage response; PCNA; protein degradation
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MDPI and ACS Style

Ticli, G.; Cazzalini, O.; Stivala, L.A.; Prosperi, E. Revisiting the Function of p21CDKN1A in DNA Repair: The Influence of Protein Interactions and Stability. Int. J. Mol. Sci. 2022, 23, 7058. https://doi.org/10.3390/ijms23137058

AMA Style

Ticli G, Cazzalini O, Stivala LA, Prosperi E. Revisiting the Function of p21CDKN1A in DNA Repair: The Influence of Protein Interactions and Stability. International Journal of Molecular Sciences. 2022; 23(13):7058. https://doi.org/10.3390/ijms23137058

Chicago/Turabian Style

Ticli, Giulio, Ornella Cazzalini, Lucia A. Stivala, and Ennio Prosperi. 2022. "Revisiting the Function of p21CDKN1A in DNA Repair: The Influence of Protein Interactions and Stability" International Journal of Molecular Sciences 23, no. 13: 7058. https://doi.org/10.3390/ijms23137058

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