Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks

Geun Hyoung Ha; Jae Hoon Ji; Sunyoung Chae; Jihyun Park; Suhyeon Kim; Jin Kwan Lee; Yonghyeon Kim; Sunwoo Min; Jeong Min Park; Tae Hong Kang; Ho Lee; Hyeseong Cho; Chang Woo Lee

doi:10.1038/s41467-019-09641-9

Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks

Geun Hyoung Ha, Jae Hoon Ji, Sunyoung Chae, Jihyun Park, Suhyeon Kim, Jin Kwan Lee, Yonghyeon Kim, Sunwoo Min, Jeong Min Park, Tae Hong Kang, Ho Lee, Hyeseong Cho, Chang Woo Lee

Producción científica: Article › revisión exhaustiva

30 Citas (Scopus)

Resumen

DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.

Idioma original	English (US)
Número de artículo	1577
Publicación	Nature communications
Volumen	10
N.º	1
DOI	https://doi.org/10.1038/s41467-019-09641-9
Estado	Published - dic 1 2019
Publicado de forma externa	Sí

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-019-09641-9

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abstract = "DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.",

author = "Ha, {Geun Hyoung} and Ji, {Jae Hoon} and Sunyoung Chae and Jihyun Park and Suhyeon Kim and Lee, {Jin Kwan} and Yonghyeon Kim and Sunwoo Min and Park, {Jeong Min} and Kang, {Tae Hong} and Ho Lee and Hyeseong Cho and Lee, {Chang Woo}",

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T1 - Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks

AU - Ha, Geun Hyoung

AU - Ji, Jae Hoon

AU - Chae, Sunyoung

AU - Park, Jihyun

AU - Kim, Suhyeon

AU - Lee, Jin Kwan

AU - Kim, Yonghyeon

AU - Min, Sunwoo

AU - Park, Jeong Min

AU - Kang, Tae Hong

AU - Lee, Ho

AU - Cho, Hyeseong

AU - Lee, Chang Woo

PY - 2019/12/1

Y1 - 2019/12/1

N2 - DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.

AB - DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.

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Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks

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