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Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair

DNA damage repair lies at the core of all cells’ survival strategy, including the survival strategy of cancerous cells. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent...

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Detalles Bibliográficos
Autores principales: Ghosh, Ishita, De Benedetti, Arrigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487508/
https://www.ncbi.nlm.nih.gov/pubmed/37686173
http://dx.doi.org/10.3390/ijms241713369
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author Ghosh, Ishita
De Benedetti, Arrigo
author_facet Ghosh, Ishita
De Benedetti, Arrigo
author_sort Ghosh, Ishita
collection PubMed
description DNA damage repair lies at the core of all cells’ survival strategy, including the survival strategy of cancerous cells. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on tousled-like kinases have brought significant clarity on the effectors of these kinases which stand to regulate DSB repair. In addition to their well-established role in DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, evidence of their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities in HRR and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation, as well as defined steps during NHEJ end processing, were earlier hints of its broadly important involvement in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors.
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spelling pubmed-104875082023-09-09 Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair Ghosh, Ishita De Benedetti, Arrigo Int J Mol Sci Review DNA damage repair lies at the core of all cells’ survival strategy, including the survival strategy of cancerous cells. Therefore, targeting such repair mechanisms forms the major goal of cancer therapeutics. The mechanism of DNA repair has been tousled with the discovery of multiple kinases. Recent studies on tousled-like kinases have brought significant clarity on the effectors of these kinases which stand to regulate DSB repair. In addition to their well-established role in DDR and cell cycle checkpoint mediation after DNA damage or inhibitors of replication, evidence of their suspected involvement in the actual DSB repair process has more recently been strengthened by the important finding that TLK1 phosphorylates RAD54 and regulates some of its activities in HRR and localization in the cell. Earlier findings of its regulation of RAD9 during checkpoint deactivation, as well as defined steps during NHEJ end processing, were earlier hints of its broadly important involvement in DSB repair. All this has opened up new avenues to target cancer cells in combination therapy with genotoxins and TLK inhibitors. MDPI 2023-08-29 /pmc/articles/PMC10487508/ /pubmed/37686173 http://dx.doi.org/10.3390/ijms241713369 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ghosh, Ishita
De Benedetti, Arrigo
Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair
title Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair
title_full Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair
title_fullStr Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair
title_full_unstemmed Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair
title_short Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair
title_sort untousling the role of tousled-like kinase 1 in dna damage repair
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487508/
https://www.ncbi.nlm.nih.gov/pubmed/37686173
http://dx.doi.org/10.3390/ijms241713369
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