Charifi Ferose, Churikov Dmitri, Eckert-Boulet Nadine, Minguet Christopher, Jourquin Frédéric, Hardy Julien, Lisby Michael, Simon Marie-Noëlle, Géli Vincent
Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille University, Institut Paoli-Calmettes, Marseille, 13009, France.
Department of Biology, University of Copenhagen, Copenhagen N, Denmark.
iScience. 2021 Feb 25;24(3):102231. doi: 10.1016/j.isci.2021.102231. eCollection 2021 Mar 19.
Functional telomeres in yeast lacking telomerase can be restored by rare Rad51- or Rad59-dependent recombination events that lead to type I and type II survivors, respectively. We previously proposed that polySUMOylation of proteins and the SUMO-targeted ubiquitin ligase Slx5-Slx8 are key factors in type II recombination. Here, we show that SUMOylation of Rad52 favors the formation of type I survivors. Conversely, preventing Rad52 SUMOylation partially bypasses the requirement of Slx5-Slx8 for type II recombination. We further report that SUMO-dependent proteasomal degradation favors type II recombination. Finally, inactivation of Rad59, but not Rad51, impairs the relocation of eroded telomeres to the Nuclear Pore complexes (NPCs). We propose that Rad59 cooperates with non-SUMOylated Rad52 to promote type II recombination at NPCs, resulting in the emergence of more robust survivors akin to ALT cancer cells. Finally, neither Rad59 nor Rad51 is required by itself for the survival of established type II survivors.
在缺乏端粒酶的酵母中，功能性端粒可以通过罕见的依赖Rad51或Rad59的重组事件得以恢复，这些事件分别导致I型和II型存活细胞的产生。我们之前提出，蛋白质的多聚SUMO化以及SUMO靶向泛素连接酶Slx5-Slx8是II型重组中的关键因素。在此，我们表明Rad52的SUMO化有利于I型存活细胞的形成。相反，阻止Rad52的SUMO化部分绕过了Slx5-Slx8对II型重组的需求。我们进一步报道，SUMO依赖的蛋白酶体降解有利于II型重组。最后，Rad59而非Rad51的失活会损害侵蚀端粒向核孔复合体（NPCs）的重新定位。我们提出，Rad59与非SUMO化的Rad52协同作用，以促进在NPCs处的II型重组，从而产生更具活力的存活细胞，类似于端粒延长替代途径（ALT）癌细胞。最后，对于已建立的II型存活细胞的存活而言，Rad59和Rad51自身都不是必需的。
