A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair

Genes & Development
Aline MarnefGaëlle Legube

Abstract

The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. DNA double-strand breaks (DSBs) within rDNA induce both rDNA transcriptional repression and nucleolar segregation, but the link between the two events remains unclear. Here we found that DSBs induced on rDNA trigger transcriptional repression in a cohesin- and HUSH (human silencing hub) complex-dependent manner throughout the cell cycle. In S/G2 cells, transcriptional repression is further followed by extended resection within the interior of the nucleolus, DSB mobilization at the nucleolar periphery within nucleolar caps, and repair by homologous recombination. We showed that nuclear envelope invaginations frequently connect the nucleolus and that rDNA DSB mobilization, but not transcriptional repression, involves the nuclear envelope-associated LINC complex and the actin pathway. Altogether, our data indicate that rDNA break localization at the nucleolar periphery is not a direct consequence of transcriptional repression but rather is an active process that shares features with the mobilization of persistent DSB in active genes and heterochromatin.

References

Jul 19, 2005·Genome Research·Sandrine CaburetAaron Bensimon
Sep 6, 2005·Science·Takehiko Kobayashi, Austen R D Ganley
Jun 7, 2011·Nature Structural & Molecular Biology·Aaron A GoodarziPenelope A Jeggo
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Danièle Hernandez-VerdunDenis L J Lafontaine
Jan 26, 2012·PLoS Genetics·Pierre CaronGaëlle Legube
Apr 14, 2012·Current Biology : CB·Dale Dorsett, Lena Ström
Aug 31, 2013·Genome Research·Ioanna FloutsakouBrian McStay
Mar 25, 2014·Nature Structural & Molecular Biology·François AymardGaëlle Legube
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Marina K AyrapetovBrendan D Price
Jun 20, 2014·Molecular Biology of the Cell·Rebecca K SwartzMegan C King
Jul 30, 2014·Nature Cell Biology·Dorthe H LarsenManuel Stucki
Oct 27, 2015·Nature Cell Biology·Taehyun RyuIrene Chiolo
Nov 7, 2015·Cell·Francisca LottersbergerTitia de Lange
Dec 22, 2015·Molecular Cell·Camille GelotBernard S Lopez
Jan 15, 2016·Journal of Cell Science·Maya SpichalEmmanuelle Fabre
Jan 19, 2016·Current Biology : CB·Hanieh FalahatiEric Wieschaus
Mar 15, 2016·Cell Reports·Daniël O WarmerdamRené H Medema
Jul 15, 2016·Journal of the Optical Society of America. A, Optics, Image Science, and Vision·Awoke NegashAnne Sentenac
Sep 30, 2016·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Michal FranekStanislav Kozubek

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Citations

Aug 29, 2020·Nucleic Acids Research·Lea Milling KorsholmDorthe Helena Larsen
Jan 21, 2021·Nucleic Acids Research·Chao DongMichael S Y Huen
Feb 2, 2021·Current Opinion in Genetics & Development·Xianrong WongColin L Stewart
Nov 4, 2020·Nature Protocols·Britta A M BouwmanNicola Crosetto
Feb 19, 2021·Nature·Coline ArnouldGaëlle Legube
Apr 11, 2021·Nature Cell Biology·Aline Marnef, Gaëlle Legube
Mar 30, 2020·Current Opinion in Cell Biology·Ioanna MitrentsiEvi Soutoglou
Apr 28, 2021·Trends in Cell Biology·Mitra Shokrollahi, Karim Mekhail
Dec 7, 2020·Current Opinion in Genetics & Development·Rebecca E Brown, Catherine H Freudenreich
May 8, 2021·Frontiers in Molecular Biosciences·Qilin LongMonika Gullerova
Jun 29, 2021·DNA Repair·Takaaki Yasuhara, Lee Zou
Mar 24, 2021·Cold Spring Harbor Perspectives in Biology·Sumit Pawar, Ulrike Kutay
Sep 25, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lydia A SibleyAndrea A Domenighetti
Oct 27, 2021·PLoS Pathogens·Michaël M MartinFlorence Margottin-Goguet

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