Ubiquitin-H2AX fusions render 53BP1 recruitment to DNA damage sites independent of RNF8 or RNF168

Article Article scientifique Article Ubiquitin-H2AX fusions render 53BP1 recruitment to DNA damage sites independent of RNF8 or RNF168 eng 2015-06-02 2015-06-02 author Kocyłowski Maciej K. Department of Molecular Biology; University of Geneva; Geneva, Switzerland author Rey Julie Andréa Alix Évelyne Department of Molecular Biology; University of Geneva; Geneva, Switzerland 927586 author Stewart Grant S. 0000-0002-0960-3241 School of Cancer Sciences; University of Birmingham; Birmingham, United Kingdom author Halazonetis Thanos 0000-0001-8384-5030 Department of Molecular Biology; University of Geneva; Geneva, Switzerland 641033 Département de biologie moléculaire et cellulaire (MOCEL) 1748-1758 10.1080/15384101.2015.1010918 25695757 1551-4005 PMC4615105 https://www.tandfonline.com/doi/full/10.1080/15384101.2015.1010918 <p>The mammalian E3 ubiquitin ligases RNF8 and RNF168 facilitate recruitment of the DNA damage response protein 53BP1 to sites of DNA double-strand breaks (DSBs). The mechanism involves recruitment of RNF8, followed by recruitment of RNF168, which ubiquitinates histones H2A/H2AX on K15. 53BP1 then binds to nucleosomes at sites of DNA DSBs by recognizing, in addition to methyl marks, histone H2A/H2AX ubiquitinated on K15. We report here that expressing H2AX fusion proteins with N-terminal bulky moieties can rescue 53BP1 recruitment to sites of DNA DSBs in cells lacking RNF8 or RNF168 or in cells treated with proteasome inhibitors, in which histone ubiquitination at sites of DNA DSBs is compromised. The rescue required S139 at the C-terminus of the H2AX fusion protein and was occasionally accompanied by partial rescue of ubiquitination at sites of DNA DSBs. We conclude that recruitment of 53BP1 to sites of DNA DSBs is possible in the absence of RNF8 or RNF168, but still dependent on chromatin ubiquitination.</p> 53BP1 RNF168 RNF8 Chromatin Ubiquitin Dewey 570 Cancer Research UK 13030 43 Département de biologie moléculaire 161 false Cell cycle 14 11 3a1aee46-694b-4fb9-8436-efb577713cdc Article (Published version) Public Article-scientifique-from-unpaywall.pdf 855928 application/pdf CC BY-NC-3.0 74ff8adcc6acd971e259eafc30f073b977f245cb42dc033a9ea97e96c605693f openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Ubiquitin-H2AX fusions render 53BP1 recruitment to DNA damage sites independent of RNF8 or RNF168	Cell cycle			2015	64	104

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Rey, Julie Andréa Alix Évelyne