NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations

Abstract Genetic information is protected against a variety of genotoxins including ionizing radiation (IR) through the DNA double-strand break (DSB) repair machinery. Genome-wide association studies and clinical sequencing of cancer patients have suggested that a number of variants in the DNA DSB r...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Keita Tomioka, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Hiromi Yanagihara, Kazumasa Fujita, Ekaterina Royba, Hiroshi Tauchi, Takashi Yamamoto, Iemasa Koh, Eiji Hirata, Yoshiki Kudo, Masao Kobayashi, Satoshi Okada, Shinya Matsuura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/48c6efd18e614b7e83decd8058014ba6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:48c6efd18e614b7e83decd8058014ba6
record_format	dspace
spelling	oai:doaj.org-article:48c6efd18e614b7e83decd8058014ba62021-12-02T17:13:18ZNBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations10.1038/s41598-021-98673-72045-2322https://doaj.org/article/48c6efd18e614b7e83decd8058014ba62021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98673-7https://doaj.org/toc/2045-2322Abstract Genetic information is protected against a variety of genotoxins including ionizing radiation (IR) through the DNA double-strand break (DSB) repair machinery. Genome-wide association studies and clinical sequencing of cancer patients have suggested that a number of variants in the DNA DSB repair genes might underlie individual differences in chromosomal radiosensitivity within human populations. However, the number of established variants that directly affect radiosensitivity is still limited. In this study, we performed whole-exome sequencing of 29 Japanese ovarian cancer patients and detected the NBS1 I171V variant, which is estimated to exist at a rate of approximately 0.15% in healthy human populations, in one patient. To clarify whether this variant indeed contributes to chromosomal radiosensitivity, we generated NBS1 I171V variant homozygous knock-in HCT116 cells and mice using the CRISPR/Cas9 system. Radiation-induced micronucleus formation and chromosomal aberration frequency were significantly increased in both HCT116 cells and mouse embryonic fibroblasts (MEFs) with knock-in of the NBS1 I171V variant compared with the levels in wild-type cells. These results suggested that the NBS1 I171V variant might be a genetic factor underlying individual differences in chromosomal radiosensitivity.Keita TomiokaTatsuo MiyamotoSilvia Natsuko AkutsuHiromi YanagiharaKazumasa FujitaEkaterina RoybaHiroshi TauchiTakashi YamamotoIemasa KohEiji HirataYoshiki KudoMasao KobayashiSatoshi OkadaShinya MatsuuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keita Tomioka Tatsuo Miyamoto Silvia Natsuko Akutsu Hiromi Yanagihara Kazumasa Fujita Ekaterina Royba Hiroshi Tauchi Takashi Yamamoto Iemasa Koh Eiji Hirata Yoshiki Kudo Masao Kobayashi Satoshi Okada Shinya Matsuura NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
description	Abstract Genetic information is protected against a variety of genotoxins including ionizing radiation (IR) through the DNA double-strand break (DSB) repair machinery. Genome-wide association studies and clinical sequencing of cancer patients have suggested that a number of variants in the DNA DSB repair genes might underlie individual differences in chromosomal radiosensitivity within human populations. However, the number of established variants that directly affect radiosensitivity is still limited. In this study, we performed whole-exome sequencing of 29 Japanese ovarian cancer patients and detected the NBS1 I171V variant, which is estimated to exist at a rate of approximately 0.15% in healthy human populations, in one patient. To clarify whether this variant indeed contributes to chromosomal radiosensitivity, we generated NBS1 I171V variant homozygous knock-in HCT116 cells and mice using the CRISPR/Cas9 system. Radiation-induced micronucleus formation and chromosomal aberration frequency were significantly increased in both HCT116 cells and mouse embryonic fibroblasts (MEFs) with knock-in of the NBS1 I171V variant compared with the levels in wild-type cells. These results suggested that the NBS1 I171V variant might be a genetic factor underlying individual differences in chromosomal radiosensitivity.
format	article
author	Keita Tomioka Tatsuo Miyamoto Silvia Natsuko Akutsu Hiromi Yanagihara Kazumasa Fujita Ekaterina Royba Hiroshi Tauchi Takashi Yamamoto Iemasa Koh Eiji Hirata Yoshiki Kudo Masao Kobayashi Satoshi Okada Shinya Matsuura
author_facet	Keita Tomioka Tatsuo Miyamoto Silvia Natsuko Akutsu Hiromi Yanagihara Kazumasa Fujita Ekaterina Royba Hiroshi Tauchi Takashi Yamamoto Iemasa Koh Eiji Hirata Yoshiki Kudo Masao Kobayashi Satoshi Okada Shinya Matsuura
author_sort	Keita Tomioka
title	NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
title_short	NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
title_full	NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
title_fullStr	NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
title_full_unstemmed	NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
title_sort	nbs1 i171v variant underlies individual differences in chromosomal radiosensitivity within human populations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/48c6efd18e614b7e83decd8058014ba6
work_keys_str_mv	AT keitatomioka nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT tatsuomiyamoto nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT silvianatsukoakutsu nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT hiromiyanagihara nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT kazumasafujita nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT ekaterinaroyba nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT hiroshitauchi nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT takashiyamamoto nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT iemasakoh nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT eijihirata nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT yoshikikudo nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT masaokobayashi nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT satoshiokada nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations AT shinyamatsuura nbs1i171vvariantunderliesindividualdifferencesinchromosomalradiosensitivitywithinhumanpopulations
_version_	1718381316154589184

NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations

Ejemplares similares