Linking spindle stability and DNA repair

Resumen de la conferencia presentada en el Barcelona BioMed Seminars el 17 de febrero de 2016.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. This signal is driven by phosphorylation events that activate both the repair of the broken DNA and the DNA damage checkpoint arrest. While phosphorylation events after DNA damage has been thoroughly studied in DDR, little is known about the role of dephosphorlation during the response. Recently, the Cdc14 phosphatase has been implicated as a key regulator of the DDR. In fact, previous results coming from our laboratory have demonstrated that this phosphatase is required to promote recombinatorial repair. However, its exact molecular function in DNA repair largely remains to be established. Here we show that in response to a DSB (double strand break) induced by the expression of the HO endonuclease, Cdc14 is release from the nucleolus and relocalize to the SPBs (Spindle Pole Bodies). We have identified Spc110, the intranuclear receptor for the ¿-tubulin complex, as a putative target of the phosphatase during the DNA damage response. After induction of a DSB, Cdc14 counterbalance the phosphorylation imposed by the Cdk over Spc110. This steady state of Spc110 phosphorylation is required for the appropriate alignment of the metaphase spindle along the bud axis of the mother cell, as well as to recruit the DSB generated to one of the SPBs. Surprisingly, disruption of the metaphase spindle impair DSB-SPB tethering and DSB repair by homologous recombination. Together, our results point to the function of Cdc14 in DNA repair by stabilizing the metaphase spindle during the formation of a DNA lesion and 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