The Yku70–Yku80 complex contributes to regulate double-strand break processing and checkpoint activation during the cell cycle

摘要

DNA double-strand breaks (DSBs) are repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). HR requires 50 DSB end degradation that occurs in the presence of cyclin-dependent kinase (CDK) activity. Here, we show that a lack of any of the NHEJ proteins Yku (Yku70–Yku80), Lif1 or DNA ligase IV (Dnl4) increases 50 DSB end degradation in G1 phase, with ykuD cells showing the strongest effect. This increase depends on MRX, the recruitment of which at DSBs is enhanced in ykuD G1 cells. DSB processing in G2 is not influenced by the absence of Yku, but it is delayed by Yku overproduction, which also decreases MRX loading on DSBs. Moreover, DSB resection in ykuD cells occurs independently of CDK activity, suggesting that it might be promoted by CDK-dependent inhibition of Yku.