Sensory Neurophysiology: Motion Vision during Motor Action

interference resulted in some cohesin loading onto meiotic chromosomes. This partial loading of cohesin resulted in similar defects in DNA repair that were now competent to activate the DNA damage checkpoint. The involvement of cohesin in the DNA damage response during a specialized cell division in which the sister chromatid is not the preferred partner in repair raises the question of what role the cohesin complex plays in DNA damage repair and checkpoint activation. The straight-forward concept that the complex holds sister chromatids in close proximity as a template for repair is not relevant in this situation. The additional observation that a fraction of cohesin on meiotic chromosomes, while not enough to support proper inter-homolog recombination, can support checkpoint activation, presents an alternative hypothesis. Cohesin may contribute to chromosome architecture in a way that promotes checkpoint activation and DNA repair independent of sister chromatid cohesion [12]. Indeed, this possibility has been suggested by experiments in mitotic vertebrate cells, in which depletion of cohesin subunits abrogated the DNA damage checkpoint in G2. However, depletion of an accessory factor required for establishment of cohesion did not alter checkpoint activation, suggesting a role independent of sister chromatid cohesion in checkpoint activation [13]. Thus, in both mitosis and meiosis, the cohesin complex may act as a molecular platform on chromosomes that promotes DNA damage checkpoint activation and DNA repair [12]. Additional questions are raised by the studies performed by Martinez-Perez and his colleagues. Since cohesin is required for the DNA damage response in meiosis, is the mechanism of its regulation the same as in mitosis? Are the same residues in the same subunits of the cohesin complex phosphorylated by checkpoint kinases in response to persistent recombination intermediates? Experiments from budding yeast suggest that this may be an oversimplification. Koshland and colleagues showed that Scc1, the mitotic kleisin, supports DSB-dependent cohesion and DNA repair in G2. However, if the meiotic kleisin, Rec8, is expressed during the mitotic cell cycle, it cannot generate cohesion in G2 and DSB repair is disrupted. They attribute this difference to a single amino acid residue in Scc1 that is phosphorylated by a DNA damage checkpoint kinase and is not conserved in Rec8 [14]. However, the SMC members of the cohesin complex are also targets of checkpoint kinases during the DNA damage response in vertebrate cells. Since it is becoming apparent that multiple organisms have more than one meiotic cohesin complex defined by different kleisin subunits, it is possible that the DNA damage checkpoint may target the common members of these meiotic complexes, Smc1 and Smc3 [4–6].