DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.

Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are two major pathways for repairing DNA double-strand breaks (DSBs); however, their respective roles in human somatic cells remain to be elucidated. Here we show using a series of human gene-knockout cell lines that NHEJ repairs nea...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Aya Kurosawa, Shinta Saito, Sairei So, Mitsumasa Hashimoto, Kuniyoshi Iwabuchi, Haruka Watabe, Noritaka Adachi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b633141a00494953826ded133b1f70c6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b633141a00494953826ded133b1f70c6
record_format	dspace
spelling	oai:doaj.org-article:b633141a00494953826ded133b1f70c62021-11-18T08:59:38ZDNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.1932-620310.1371/journal.pone.0072253https://doaj.org/article/b633141a00494953826ded133b1f70c62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23967291/?tool=EBIhttps://doaj.org/toc/1932-6203Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are two major pathways for repairing DNA double-strand breaks (DSBs); however, their respective roles in human somatic cells remain to be elucidated. Here we show using a series of human gene-knockout cell lines that NHEJ repairs nearly all of the topoisomerase II- and low-dose radiation-induced DNA damage, while it negatively affects survival of cells harbouring replication-associated DSBs. Intriguingly, we find that loss of DNA ligase IV, a critical NHEJ ligase, and Artemis, an NHEJ factor with endonuclease activity, independently contribute to increased resistance to replication-associated DSBs. We also show that loss of Artemis alleviates hypersensitivity of DNA ligase IV-null cells to low-dose radiation- and topoisomerase II-induced DSBs. Finally, we demonstrate that Artemis-null human cells display increased gene-targeting efficiencies, particularly in the absence of DNA ligase IV. Collectively, these data suggest that DNA ligase IV and Artemis act cooperatively to promote NHEJ, thereby suppressing HR. Our results point to the possibility that HR can only operate on accidental DSBs when NHEJ is missing or abortive, and Artemis may be involved in pathway switching from incomplete NHEJ to HR.Aya KurosawaShinta SaitoSairei SoMitsumasa HashimotoKuniyoshi IwabuchiHaruka WatabeNoritaka AdachiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72253 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aya Kurosawa Shinta Saito Sairei So Mitsumasa Hashimoto Kuniyoshi Iwabuchi Haruka Watabe Noritaka Adachi DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.
description	Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are two major pathways for repairing DNA double-strand breaks (DSBs); however, their respective roles in human somatic cells remain to be elucidated. Here we show using a series of human gene-knockout cell lines that NHEJ repairs nearly all of the topoisomerase II- and low-dose radiation-induced DNA damage, while it negatively affects survival of cells harbouring replication-associated DSBs. Intriguingly, we find that loss of DNA ligase IV, a critical NHEJ ligase, and Artemis, an NHEJ factor with endonuclease activity, independently contribute to increased resistance to replication-associated DSBs. We also show that loss of Artemis alleviates hypersensitivity of DNA ligase IV-null cells to low-dose radiation- and topoisomerase II-induced DSBs. Finally, we demonstrate that Artemis-null human cells display increased gene-targeting efficiencies, particularly in the absence of DNA ligase IV. Collectively, these data suggest that DNA ligase IV and Artemis act cooperatively to promote NHEJ, thereby suppressing HR. Our results point to the possibility that HR can only operate on accidental DSBs when NHEJ is missing or abortive, and Artemis may be involved in pathway switching from incomplete NHEJ to HR.
format	article
author	Aya Kurosawa Shinta Saito Sairei So Mitsumasa Hashimoto Kuniyoshi Iwabuchi Haruka Watabe Noritaka Adachi
author_facet	Aya Kurosawa Shinta Saito Sairei So Mitsumasa Hashimoto Kuniyoshi Iwabuchi Haruka Watabe Noritaka Adachi
author_sort	Aya Kurosawa
title	DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.
title_short	DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.
title_full	DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.
title_fullStr	DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.
title_full_unstemmed	DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.
title_sort	dna ligase iv and artemis act cooperatively to suppress homologous recombination in human cells: implications for dna double-strand break repair.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b633141a00494953826ded133b1f70c6
work_keys_str_mv	AT ayakurosawa dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair AT shintasaito dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair AT saireiso dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair AT mitsumasahashimoto dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair AT kuniyoshiiwabuchi dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair AT harukawatabe dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair AT noritakaadachi dnaligaseivandartemisactcooperativelytosuppresshomologousrecombinationinhumancellsimplicationsfordnadoublestrandbreakrepair
_version_	1718421044795015168

DNA ligase IV and artemis act cooperatively to suppress homologous recombination in human cells: implications for DNA double-strand break repair.

Ejemplares similares