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An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea

While bacteria and eukaryotes show distinct mechanisms of DNA damage response (DDR) regulation, investigation of ultraviolet (UV)-responsive expression in a few archaea did not yield any conclusive evidence for an archaeal DDR regulatory network. Nevertheless, expression of Orc1-2, an ortholog of th...

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Autores principales: Sun, Mengmeng, Feng, Xu, Liu, Zhenzhen, Han, Wenyuan, Liang, Yun Xiang, She, Qunxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061795/
https://www.ncbi.nlm.nih.gov/pubmed/29878182
http://dx.doi.org/10.1093/nar/gky487
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author Sun, Mengmeng
Feng, Xu
Liu, Zhenzhen
Han, Wenyuan
Liang, Yun Xiang
She, Qunxin
author_facet Sun, Mengmeng
Feng, Xu
Liu, Zhenzhen
Han, Wenyuan
Liang, Yun Xiang
She, Qunxin
author_sort Sun, Mengmeng
collection PubMed
description While bacteria and eukaryotes show distinct mechanisms of DNA damage response (DDR) regulation, investigation of ultraviolet (UV)-responsive expression in a few archaea did not yield any conclusive evidence for an archaeal DDR regulatory network. Nevertheless, expression of Orc1-2, an ortholog of the archaeal origin recognition complex 1/cell division control protein 6 (Orc1/Cdc6) superfamily proteins was strongly activated in Sulfolobus solfataricus and Sulfolobus acidocaldarius upon UV irradiation. Here, a series of experiments were conducted to investigate the possible functions of Orc1-2 in DNA damage repair in Sulfolobus islandicus. Study of DDR in Δorc1-2 revealed that Orc1-2 deficiency abolishes DNA damage-induced differential expression of a large number of genes and the mutant showed hypersensitivity to DNA damage treatment. Reporter gene and DNase I footprinting assays demonstrated that Orc1-2 interacts with a conserved hexanucleotide motif present in several DDR gene promoters and regulates their expression. Manipulation of orc1-2 expression by promoter substitution in this archaeon revealed that a high level of orc1-2 expression is essential but not sufficient to trigger DDR. Together, these results have placed Orc1-2 in the heart of the archaeal DDR regulation, and the resulting Orc1-2-centered regulatory circuit represents the first DDR network identified in Archaea, the third domain of life.
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spelling pubmed-60617952018-08-07 An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea Sun, Mengmeng Feng, Xu Liu, Zhenzhen Han, Wenyuan Liang, Yun Xiang She, Qunxin Nucleic Acids Res Genome Integrity, Repair and Replication While bacteria and eukaryotes show distinct mechanisms of DNA damage response (DDR) regulation, investigation of ultraviolet (UV)-responsive expression in a few archaea did not yield any conclusive evidence for an archaeal DDR regulatory network. Nevertheless, expression of Orc1-2, an ortholog of the archaeal origin recognition complex 1/cell division control protein 6 (Orc1/Cdc6) superfamily proteins was strongly activated in Sulfolobus solfataricus and Sulfolobus acidocaldarius upon UV irradiation. Here, a series of experiments were conducted to investigate the possible functions of Orc1-2 in DNA damage repair in Sulfolobus islandicus. Study of DDR in Δorc1-2 revealed that Orc1-2 deficiency abolishes DNA damage-induced differential expression of a large number of genes and the mutant showed hypersensitivity to DNA damage treatment. Reporter gene and DNase I footprinting assays demonstrated that Orc1-2 interacts with a conserved hexanucleotide motif present in several DDR gene promoters and regulates their expression. Manipulation of orc1-2 expression by promoter substitution in this archaeon revealed that a high level of orc1-2 expression is essential but not sufficient to trigger DDR. Together, these results have placed Orc1-2 in the heart of the archaeal DDR regulation, and the resulting Orc1-2-centered regulatory circuit represents the first DDR network identified in Archaea, the third domain of life. Oxford University Press 2018-07-27 2018-06-07 /pmc/articles/PMC6061795/ /pubmed/29878182 http://dx.doi.org/10.1093/nar/gky487 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Sun, Mengmeng
Feng, Xu
Liu, Zhenzhen
Han, Wenyuan
Liang, Yun Xiang
She, Qunxin
An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea
title An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea
title_full An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea
title_fullStr An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea
title_full_unstemmed An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea
title_short An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea
title_sort orc1/cdc6 ortholog functions as a key regulator in the dna damage response in archaea
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061795/
https://www.ncbi.nlm.nih.gov/pubmed/29878182
http://dx.doi.org/10.1093/nar/gky487
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