SIRT6 is a DNA double-strand break sensor

DNA double-strand breaks (DSB) are the most deleterious type of DNA damage. In this work, we show that SIRT6 directly recognizes DNA damage through a tunnel-like structure that has high affinity for DSB. SIRT6 relocates to sites of damage independently of signaling and known sensors. It activates do...

Full description

Bibliographic Details
Main Authors:	Lior Onn, Miguel Portillo, Stefan Ilic, Gal Cleitman, Daniel Stein, Shai Kaluski, Ido Shirat, Zeev Slobodnik, Monica Einav, Fabian Erdel, Barak Akabayov, Debra Toiber
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2020-01-01
Series:	eLife
Subjects:	SIRT6 DNA damage sensor DSB DNA repair
Online Access:	https://elifesciences.org/articles/51636

id	doaj-8ec54c204be64101928f8e9ebb75bef6
record_format	Article
spelling	doaj-8ec54c204be64101928f8e9ebb75bef62021-05-05T20:47:03ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.51636SIRT6 is a DNA double-strand break sensorLior Onn0Miguel Portillo1Stefan Ilic2Gal Cleitman3Daniel Stein4Shai Kaluski5Ido Shirat6Zeev Slobodnik7Monica Einav8Fabian Erdel9https://orcid.org/0000-0003-2888-7777Barak Akabayov10https://orcid.org/0000-0002-3882-2742Debra Toiber11https://orcid.org/0000-0002-1465-0130Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDivision of Chromatin Networks, German Cancer Research Center (DKFZ), BioQuant, Heidelberg, Germany; Centre de Biologie Intégrative, CNRS UPS, Toulouse, FranceDepartment of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel; The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDNA double-strand breaks (DSB) are the most deleterious type of DNA damage. In this work, we show that SIRT6 directly recognizes DNA damage through a tunnel-like structure that has high affinity for DSB. SIRT6 relocates to sites of damage independently of signaling and known sensors. It activates downstream signaling for DSB repair by triggering ATM recruitment, H2AX phosphorylation and the recruitment of proteins of the homologous recombination and non-homologous end joining pathways. Our findings indicate that SIRT6 plays a previously uncharacterized role as a DNA damage sensor, a critical factor in initiating the DNA damage response (DDR). Moreover, other Sirtuins share some DSB-binding capacity and DDR activation. SIRT6 activates the DDR before the repair pathway is chosen, and prevents genomic instability. Our findings place SIRT6 as a sensor of DSB, and pave the road to dissecting the contributions of distinct DSB sensors in downstream signaling.https://elifesciences.org/articles/51636SIRT6DNA damagesensorDSBDNA repair
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Lior Onn Miguel Portillo Stefan Ilic Gal Cleitman Daniel Stein Shai Kaluski Ido Shirat Zeev Slobodnik Monica Einav Fabian Erdel Barak Akabayov Debra Toiber
spellingShingle	Lior Onn Miguel Portillo Stefan Ilic Gal Cleitman Daniel Stein Shai Kaluski Ido Shirat Zeev Slobodnik Monica Einav Fabian Erdel Barak Akabayov Debra Toiber SIRT6 is a DNA double-strand break sensor eLife SIRT6 DNA damage sensor DSB DNA repair
author_facet	Lior Onn Miguel Portillo Stefan Ilic Gal Cleitman Daniel Stein Shai Kaluski Ido Shirat Zeev Slobodnik Monica Einav Fabian Erdel Barak Akabayov Debra Toiber
author_sort	Lior Onn
title	SIRT6 is a DNA double-strand break sensor
title_short	SIRT6 is a DNA double-strand break sensor
title_full	SIRT6 is a DNA double-strand break sensor
title_fullStr	SIRT6 is a DNA double-strand break sensor
title_full_unstemmed	SIRT6 is a DNA double-strand break sensor
title_sort	sirt6 is a dna double-strand break sensor
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2020-01-01
description	DNA double-strand breaks (DSB) are the most deleterious type of DNA damage. In this work, we show that SIRT6 directly recognizes DNA damage through a tunnel-like structure that has high affinity for DSB. SIRT6 relocates to sites of damage independently of signaling and known sensors. It activates downstream signaling for DSB repair by triggering ATM recruitment, H2AX phosphorylation and the recruitment of proteins of the homologous recombination and non-homologous end joining pathways. Our findings indicate that SIRT6 plays a previously uncharacterized role as a DNA damage sensor, a critical factor in initiating the DNA damage response (DDR). Moreover, other Sirtuins share some DSB-binding capacity and DDR activation. SIRT6 activates the DDR before the repair pathway is chosen, and prevents genomic instability. Our findings place SIRT6 as a sensor of DSB, and pave the road to dissecting the contributions of distinct DSB sensors in downstream signaling.
topic	SIRT6 DNA damage sensor DSB DNA repair
url	https://elifesciences.org/articles/51636
work_keys_str_mv	AT lioronn sirt6isadnadoublestrandbreaksensor AT miguelportillo sirt6isadnadoublestrandbreaksensor AT stefanilic sirt6isadnadoublestrandbreaksensor AT galcleitman sirt6isadnadoublestrandbreaksensor AT danielstein sirt6isadnadoublestrandbreaksensor AT shaikaluski sirt6isadnadoublestrandbreaksensor AT idoshirat sirt6isadnadoublestrandbreaksensor AT zeevslobodnik sirt6isadnadoublestrandbreaksensor AT monicaeinav sirt6isadnadoublestrandbreaksensor AT fabianerdel sirt6isadnadoublestrandbreaksensor AT barakakabayov sirt6isadnadoublestrandbreaksensor AT debratoiber sirt6isadnadoublestrandbreaksensor
_version_	1721458588258402304

SIRT6 is a DNA double-strand break sensor

Similar Items