Figure 7.

Model for Pol ε function in plant DDR. A, In the wild type, Pol ε catalytic subunit POL2A is involved in replication stress sensing; this leads to ATR-dependent activation of the WEE1 and SOG1 pathways, allowing the expression of genes involved in cell cycle arrest, DNA repair, and nucleotide biosynthesis, ultimately leading to fork stabilization and completion of DNA replication and cell survival. B, In pol2A mutants with point mutations affecting POL2A activity, the abnormal Pol ε subunit likely gums up replication, leading to constitutive replication stress and activating ATR. The WEE1 branch of the downstream pathway is essential to plant survival, whereas the SOG1 branch of the pathway is dispensable, but confers tolerance to replicative stress. SOG1 activation may also negatively regulate ATM signaling leading to enhanced sensitivity to DNA damaging agents. C, When accumulation of POL2A is reduced, Pol δ likely replaces it and replicates both DNA strands. In the absence of Pol ε, replicative stress signaling is not properly activated, which may lead to fork collapse and DNA lesions that can in turn activate ATM signaling and promote tolerance to DSB-inducing agents. In all panels, dashed arrows indicate putative pathways that remain to be molecularly identified.