The spindle-stabilizing function of Cdc14 is required to promote recombinatorial DNA repair

Póster presentado al XL Congreso de la Sociedad Española de Genética, celebrado en Córdoba del 16 al 18 de septiembre de 2015.Endogenous or exogenous agents that cause genotoxic stress are constantly threatening the genomes of all organisms. In response to a DNA lesion, different processes (collectively known as DDR) are triggered in order to coordinate the repair of the damage with cell cycle progression. While phosphorylation events after DNA damage have been thoroughly studied in the DDR, little is known about the role of dephosphorylation during the response. Previous data coming from our group have revealed the importance of the phosphatase Cdc14 in promoting recombinational DNA repair. Here we show that in response to a DSB (double strand break) induced by the expression of the HO endonuclease, cells block in G2/M with a metaphase spindle aligned along the bud axis. Under this arrest, the DNA break is actively recruited to one of the SPBs (Spindle Pole Bodies). Inactivation of the phosphatase activity causes continuous misalignment of the metaphase spindle, increases oscillatory SPBs movements and impairs DSB-SPB tethering. All these phenotypes can be mimicked in a wild-type strain just by adding the microtubule depolymerizing drug nocodazole or by inactivating Spc110, a component of the SPB and a Cdc14 target during the DDR. Surprisingly, these phenotypes are directly linked to DNA repair, since both nocodazole treatment and lack of Spc110 activity impair DSB repair by HR to the same extent as cdc14-1 mutants. Together, our results point to the function of Cdc14 in DNA repair by promoting SPB stabilization and SPB-DSB interaction, and suggest that the relocation of damage sites to the SPBs plays an important role in a naturally occurring repair process that minimizes genome instability.Peer Reviewe