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Genetics. 2019 Sep 18. pii: genetics.302580.2019. doi: 10.1534/genetics.119.302580. [Epub ahead of print]

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

Author information

1
CSIC-University of Seville-University Pablo de Olavide.
2
CSIC-University of Seville-University Pablo de Olavide felix.prado@cabimer.es.

Abstract

The accuracy of most DNA processes depends on chromatin integrity and dynamics. Our analyses in the yeast Saccharomyces cerevisiae show that the absence of Swr1 (the catalytic and scaffold subunit of the chromatin remodeling complex SWR) leads to the formation of long-duration Rad52 - 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 DSBs, hydroxyurea, 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 (mps3Δ75-150 and src1Δ); 2) actin and actin regulators (act1-157, act1-159, crn1Δ and cdc42-6); or 3) the SWR subunit Swc5 and the SWR substrate Htz1. However, they are not suppressed by global disruption of actin filaments or by the absence of Csm4 (a component of the external nuclear membrane that forms a bridging complex, LINC, with Mps3, thus connecting the actin cytoskeleton with chromatin). Moreover, swr1Δ-induced Rad52 foci and intramolecular recombination are not associated with tethering recombinogenic DNA lesions to the nuclear periphery. In conclusion, the absence of Swr1 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 HR of actin-containing complexes.

KEYWORDS:

Mps3; Swr1; actin; homologous recombination; nuclear envelope

PMID:
31533921
DOI:
10.1534/genetics.119.302580
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