Actin and Nuclear Envelope Components Influence Ectopic Recombination in the Absence of Swr1.

The accuracy of most DNA processes depends on chromatin integrity and dynamics. Our analyses in the yeast Saccharomyces cerevisiae show that an absence of (the catalytic and scaffold subunit of the chromatin-remodeling complex SWR) leads to the formation of long-duration , but not RPA, foci and to an increase in intramolecular recombination. These phenotypes are further increased by MMS, zeocin, and ionizing radiation, but not by double-strand breaks, HU, or transcription/replication collisions, suggesting that they are associated with specific DNA lesions. Importantly, these phenotypes can be specifically suppressed by mutations in: (1) chromatin-anchorage internal nuclear membrane components ( increment 75-150 and increment ); (2) actin and actin regulators (-157, -159, increment , and -6); or (3) the SWR subunit and the SWR substrate . However, they are not suppressed by global disruption of actin filaments or by the absence of (a component of the external nuclear membrane that forms a bridging complex with , thus connecting the actin cytoskeleton with chromatin). Moreover, increment -induced foci and intramolecular recombination are not associated with tethering recombinogenic DNA lesions to the nuclear periphery. In conclusion, the absence of impairs efficient recombinational repair of specific DNA lesions by mechanisms that are influenced by SWR subunits, including actin, and nuclear envelope components. We suggest that these recombinational phenotypes might be associated with a pathological effect on homologous recombination of actin-containing complexes.