Tenorio-Gómez María, de Sena-Tomás Carmen, Pérez-Martín Jose
Instituto de Biología Funcional y Genómica (CSIC), Salamanca, Spain.
PLoS One. 2015 Sep 14;10(9):e0137192. doi: 10.1371/journal.pone.0137192. eCollection 2015.
DNA damage response (DDR) leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation.
DNA损伤反应(DDR)会引发DNA修复,并根据损伤程度引发包括细胞死亡在内的进一步事件。有证据表明,细胞分化也可能是DDR的结果。在植物致病真菌玉米黑粉菌感染菌丝的形成过程中,两种DDR激酶Atr1和Chk1需要诱导G2期细胞周期停滞,而这反过来对于展现毒力程序至关重要。然而,这一过程中DDR的触发因素一直难以捉摸。在本报告中,我们提供的数据表明,在玉米黑粉菌感染丝形成过程中,DDR的激活与DNA损伤无关。我们分析了感染丝形成过程中的总体DNA复制情况,未发现DNA复制受损的迹象。此外,使用RPA-GFP融合蛋白作为DNA损伤存在的替代标志物,我们在细胞水平上未能检测到任何DNA损伤迹象。另外,对于上述细胞周期停滞的诱导以及毒力而言,传递DNA损伤信号的关键物质MRN和9-1-1复合物都不是必需的。相反,我们发现,在其他系统中作为Atr1和Chk1支架的类 claspin 蛋白Mrc1,在这两个过程中都是必需的。我们讨论了在玉米黑粉菌毒力程序激活过程中,独立于DNA损伤触发DDR的可能替代方式。