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The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate

Human HLTF participates in the lesion-bypass mechanism through the fork reversal structure, known as template switching of post-replication repair. However, the mechanism by which HLTF promotes the replication progression and fork stability of damaged forks remains unclear. Here, we identify a novel...

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Autores principales: Shiu, Jia-Lin, Wu, Cheng-Kuei, Chang, Song-Bin, Sun, Yan-Jhih, Chen, Yen-Ju, Lai, Chien-Chen, Chiu, Wen-Tai, Chang, Wen-Tsan, Myung, Kyungjae, Su, Wen-Pin, Liaw, Hungjiun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719709/
https://www.ncbi.nlm.nih.gov/pubmed/33281189
http://dx.doi.org/10.1038/s41389-020-00289-5
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author Shiu, Jia-Lin
Wu, Cheng-Kuei
Chang, Song-Bin
Sun, Yan-Jhih
Chen, Yen-Ju
Lai, Chien-Chen
Chiu, Wen-Tai
Chang, Wen-Tsan
Myung, Kyungjae
Su, Wen-Pin
Liaw, Hungjiun
author_facet Shiu, Jia-Lin
Wu, Cheng-Kuei
Chang, Song-Bin
Sun, Yan-Jhih
Chen, Yen-Ju
Lai, Chien-Chen
Chiu, Wen-Tai
Chang, Wen-Tsan
Myung, Kyungjae
Su, Wen-Pin
Liaw, Hungjiun
author_sort Shiu, Jia-Lin
collection PubMed
description Human HLTF participates in the lesion-bypass mechanism through the fork reversal structure, known as template switching of post-replication repair. However, the mechanism by which HLTF promotes the replication progression and fork stability of damaged forks remains unclear. Here, we identify a novel protein–protein interaction between HLTF and PARP1. The depletion of HLTF and PARP1 increases chromosome breaks, further reduces the length of replication tracks, and concomitantly increases the number of stalled forks after methyl methanesulfonate treatment according to a DNA fiber analysis. The progression of replication also depends on BARD1 in the presence of MMS treatment. By combining 5-ethynyl-2′-deoxyuridine with a proximity ligation assay, we revealed that the HLTF, PARP1, and BRCA1/BARD1/RAD51 proteins were initially recruited to damaged forks. However, prolonged stalling of damaged forks results in fork collapse. HLTF and PCNA dissociate from the collapsed forks, with increased accumulation of PARP1 and BRCA1/BARD1/RAD51 at the collapsed forks. Our results reveal that HLTF together with PARP1 and BARD1 participates in the stabilization of damaged forks, and the PARP1–BARD1 interaction is further involved in the repair of collapse forks.
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spelling pubmed-77197092020-12-11 The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate Shiu, Jia-Lin Wu, Cheng-Kuei Chang, Song-Bin Sun, Yan-Jhih Chen, Yen-Ju Lai, Chien-Chen Chiu, Wen-Tai Chang, Wen-Tsan Myung, Kyungjae Su, Wen-Pin Liaw, Hungjiun Oncogenesis Article Human HLTF participates in the lesion-bypass mechanism through the fork reversal structure, known as template switching of post-replication repair. However, the mechanism by which HLTF promotes the replication progression and fork stability of damaged forks remains unclear. Here, we identify a novel protein–protein interaction between HLTF and PARP1. The depletion of HLTF and PARP1 increases chromosome breaks, further reduces the length of replication tracks, and concomitantly increases the number of stalled forks after methyl methanesulfonate treatment according to a DNA fiber analysis. The progression of replication also depends on BARD1 in the presence of MMS treatment. By combining 5-ethynyl-2′-deoxyuridine with a proximity ligation assay, we revealed that the HLTF, PARP1, and BRCA1/BARD1/RAD51 proteins were initially recruited to damaged forks. However, prolonged stalling of damaged forks results in fork collapse. HLTF and PCNA dissociate from the collapsed forks, with increased accumulation of PARP1 and BRCA1/BARD1/RAD51 at the collapsed forks. Our results reveal that HLTF together with PARP1 and BARD1 participates in the stabilization of damaged forks, and the PARP1–BARD1 interaction is further involved in the repair of collapse forks. Nature Publishing Group UK 2020-12-07 /pmc/articles/PMC7719709/ /pubmed/33281189 http://dx.doi.org/10.1038/s41389-020-00289-5 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shiu, Jia-Lin
Wu, Cheng-Kuei
Chang, Song-Bin
Sun, Yan-Jhih
Chen, Yen-Ju
Lai, Chien-Chen
Chiu, Wen-Tai
Chang, Wen-Tsan
Myung, Kyungjae
Su, Wen-Pin
Liaw, Hungjiun
The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
title The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
title_full The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
title_fullStr The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
title_full_unstemmed The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
title_short The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
title_sort hltf–parp1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719709/
https://www.ncbi.nlm.nih.gov/pubmed/33281189
http://dx.doi.org/10.1038/s41389-020-00289-5
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