Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1785103260321841152 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10487508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT ghoshishita untouslingtheroleoftousledlikekinase1indnadamagerepair AT debenedettiarrigo untouslingtheroleoftousledlikekinase1indnadamagerepair |