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DNA–protein cross-link repair: what do we know now?
When a protein is covalently and irreversibly bound to DNA (i.e., a DNA–protein cross-link [DPC]), it may obstruct any DNA-based transaction, such as transcription and replication. DPC formation is very common in cells, as it can arise from endogenous factors, such as aldehyde produced during cell m...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945406/ https://www.ncbi.nlm.nih.gov/pubmed/31921408 http://dx.doi.org/10.1186/s13578-019-0366-z |
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author | Zhang, Huimin Xiong, Yun Chen, Junjie |
author_facet | Zhang, Huimin Xiong, Yun Chen, Junjie |
author_sort | Zhang, Huimin |
collection | PubMed |
description | When a protein is covalently and irreversibly bound to DNA (i.e., a DNA–protein cross-link [DPC]), it may obstruct any DNA-based transaction, such as transcription and replication. DPC formation is very common in cells, as it can arise from endogenous factors, such as aldehyde produced during cell metabolism, or exogenous sources like ionizing radiation, ultraviolet light, and chemotherapeutic agents. DPCs are composed of DNA, protein, and their cross-linked bonds, each of which can be targeted by different repair pathways. Many studies have demonstrated that nucleotide excision repair and homologous recombination can act on DNA molecules and execute nuclease-dependent DPC repair. Enzymes that have evolved to deal specifically with DPC, such as tyrosyl-DNA phosphodiesterases 1 and 2, can directly reverse cross-linked bonds and release DPC from DNA. The newly identified proteolysis pathway, which employs the proteases Wss1 and SprT-like domain at the N-terminus (SPRTN), can directly hydrolyze the proteins in DPCs, thus offering a new venue for DPC repair in cells. A deep understanding of the mechanisms of each pathway and the interplay among them may provide new guidance for targeting DPC repair as a therapeutic strategy for cancer. Here, we summarize the progress in DPC repair field and describe how cells may employ these different repair pathways for efficient repair of DPCs. |
format | Online Article Text |
id | pubmed-6945406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69454062020-01-09 DNA–protein cross-link repair: what do we know now? Zhang, Huimin Xiong, Yun Chen, Junjie Cell Biosci Review When a protein is covalently and irreversibly bound to DNA (i.e., a DNA–protein cross-link [DPC]), it may obstruct any DNA-based transaction, such as transcription and replication. DPC formation is very common in cells, as it can arise from endogenous factors, such as aldehyde produced during cell metabolism, or exogenous sources like ionizing radiation, ultraviolet light, and chemotherapeutic agents. DPCs are composed of DNA, protein, and their cross-linked bonds, each of which can be targeted by different repair pathways. Many studies have demonstrated that nucleotide excision repair and homologous recombination can act on DNA molecules and execute nuclease-dependent DPC repair. Enzymes that have evolved to deal specifically with DPC, such as tyrosyl-DNA phosphodiesterases 1 and 2, can directly reverse cross-linked bonds and release DPC from DNA. The newly identified proteolysis pathway, which employs the proteases Wss1 and SprT-like domain at the N-terminus (SPRTN), can directly hydrolyze the proteins in DPCs, thus offering a new venue for DPC repair in cells. A deep understanding of the mechanisms of each pathway and the interplay among them may provide new guidance for targeting DPC repair as a therapeutic strategy for cancer. Here, we summarize the progress in DPC repair field and describe how cells may employ these different repair pathways for efficient repair of DPCs. BioMed Central 2020-01-07 /pmc/articles/PMC6945406/ /pubmed/31921408 http://dx.doi.org/10.1186/s13578-019-0366-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Zhang, Huimin Xiong, Yun Chen, Junjie DNA–protein cross-link repair: what do we know now? |
title | DNA–protein cross-link repair: what do we know now? |
title_full | DNA–protein cross-link repair: what do we know now? |
title_fullStr | DNA–protein cross-link repair: what do we know now? |
title_full_unstemmed | DNA–protein cross-link repair: what do we know now? |
title_short | DNA–protein cross-link repair: what do we know now? |
title_sort | dna–protein cross-link repair: what do we know now? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945406/ https://www.ncbi.nlm.nih.gov/pubmed/31921408 http://dx.doi.org/10.1186/s13578-019-0366-z |
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