Small RNAs Recruit Chromatin-Modifying Enzymes MMSET and Tip60 to Reconfigure Damaged DNA upon Double-Strand Break and Facilitate Repair

Cancer Research
Qinhong Wang, Michael Goldstein

Abstract

Recent reports have demonstrated that DNA double-strand break (DSB)-induced small RNAs (diRNA) play an important role in the DNA damage response (DDR). However, the molecular mechanism by which diRNAs regulate the DDR remains unclear. Here, we report that Dicer- and Drosha-dependent diRNAs function as guiding molecules to promote the recruitment of the methyltransferase MMSET (WHSC1) and the acetyltransferase Tip60 (KAT5) to the DSB, where local levels of histone H4 di- and tri-methylation at lysine 20 (H4K20me2, 3) and H4 acetylation at lysine 16 (H4K16Ac) were enhanced. These histone modification events resulted in an open, flexible chromatin configuration, as indicated by the increased release of histones γH2AX, H2AX, and H3 from damaged chromatin. Furthermore, we found that diRNA-associated AGO2 interacted with MMSET and Tip60 and that the diRNA binding and catalytic activities of AGO2 were dispensable for the interaction but required for the recruitment of MMSET and Tip60 to DSBs. Consequently, diRNA-mediated chromatin remodeling promoted DSB repair by enhancing the recruitment of Rad51 and BRCA1 to the DSB site. Taken together, our findings reveal an unexpected direct role for diRNAs in regulating chromatin remodeling to ...Continue Reading

References

Oct 29, 1999·Genes & Development·A J PierceM Jasin
Oct 3, 2002·Cellular Signalling·Fayza DaboussiBernard S Lopez
Sep 26, 2003·Nature·Yoontae LeeV Narry Kim
Nov 5, 2004·Nature·Yentram HuyenThanos D Halazonetis
Jan 5, 2006·Genes & Development·Roger A GreenbergDavid M Livingston
Feb 14, 2006·Science·Michael Shogren-KnaakCraig L Peterson
Jan 27, 2007·The EMBO Journal·Young-Kook Kim, V Narry Kim
May 9, 2007·Nature Cell Biology·Elijahu BerkovichMichael B Kastan
Feb 26, 2009·Cell·Richard W Carthew, Erik J Sontheimer
Oct 8, 2009·The Journal of Biological Chemistry·Yan LiDanny Reinberg
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Nov 4, 2009·Nature Cell Biology·Wolfgang Fischle
Feb 18, 2010·Cell Cycle·Yingli SunBrendan D Price
Apr 17, 2010·Trends in Biochemical Sciences·Tomoko Kawamata, Yukihide Tomari
Oct 23, 2010·Molecular Cell·Alberto Ciccia, Stephen J Elledge
Jan 8, 2011·Cell Cycle·Ye Xu, Brendan D Price
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ildiko HajduStephen J Elledge
Mar 21, 2012·Cellular and Molecular Life Sciences : CMLS·Cecil HanXiongbin Lu
Jun 23, 2012·Nature·Sofia FranciaFabrizio d'Adda di Fagagna
Mar 19, 2013·Cell·Brendan D Price, Alan D D'Andrea

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Citations

Nov 9, 2016·Journal of Molecular Biology·Giuseppina D'Alessandro, Fabrizio d'Adda di Fagagna
Feb 24, 2017·The FEBS Journal·Ilaria CapozzoFabrizio d'Adda di Fagagna
Dec 14, 2017·The Journal of Cell Biology·Shalaka Chitale, Holger Richly
Feb 26, 2016·Journal of Cell Science·Sofia FranciaFabrizio d'Adda di Fagagna
Jun 24, 2017·The Journal of Cell Biology·Kaspar BurgerMonika Gullerova
Oct 12, 2018·The Journal of Clinical Investigation·Motoko UnokiHiroyuki Sasaki
Jan 30, 2019·Cellular and Molecular Life Sciences : CMLS·Wen-Ting Guo, Yangming Wang
Feb 28, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Judit Domingo-PrimNeus Visa
Mar 14, 2020·Critical Reviews in Biochemistry and Molecular Biology·Xiaojing LiQubo Zhu
Feb 14, 2020·Nature Reviews. Genetics·Michael J Gutbrod, Robert A Martienssen
Jul 20, 2019·Oncotarget·Michalis FragkosArnaud Coquelle
Apr 13, 2017·Nucleic Acids Research·Shalaka Chitale, Holger Richly
Oct 28, 2017·Science China. Life Sciences·Jian OuyangLee Zou
Dec 19, 2018·Nature Communications·Giuseppina D'AlessandroFabrizio d'Adda di Fagagna
Aug 9, 2020·Nature Reviews. Genetics·Dali ZongAndré Nussenzweig
Feb 25, 2017·Cell Death and Differentiation·Ben R HawleyMartin Bushell
Aug 26, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Anne K Voss, Tim Thomas
Nov 1, 2020·International Journal of Molecular Sciences·Iwona Rzeszutek, Gabriela Betlej
Jan 2, 2021·Progress in Biophysics and Molecular Biology·Luke A Yates
Mar 7, 2021·Cancers·Iwona Nowak, Aishe A Sarshad
Feb 6, 2018·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Shunrong JiXianjun Yu
Sep 14, 2020·DNA Repair·Cathrine Broberg Vågbø, Geir Slupphaug
May 1, 2021·Biomolecules·Matvey Mikhailovich MurashkoDenis Eriksonovich Demin
May 4, 2021·Nucleic Acids Research·Monica ManciniIan Marc Bonapace
May 25, 2021·Frontiers in Molecular Biosciences·Julie A KlaricStephanie Panier
Mar 31, 2018·Chemical Reviews·Flavia MicheliniFabrizio d'Adda di Fagagna

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