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Originally published as Genetics Published Articles Ahead of Print on March 31, 2005.

Genetics, Vol. 170, 519-531, June 2005, Copyright © 2005
doi:10.1534/genetics.104.037598

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A Postsynaptic Role for Rhp55/57 That Is Responsible for Cell Death in {Delta}rqh1 Mutants Following Replication Arrest in Schizosaccharomyces pombe

Justin C. Hope*, Mohamed Maftahi{dagger} and Greg A. Freyer*,{dagger},1

* Graduate Program in Anatomy and Cell Biology, Department of Anatomy and Cell Biology
{dagger} Department of Environmental Health Sciences, Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032

1 Corresponding author: Kolb Bldg., Room 140, Columbia University, 722 W. 168th St., New York, NY 10032.
E-mail: gaf1{at}columbia.edu

Following replication arrest, multiple cellular responses are triggered to maintain genomic integrity. In fission yeast, the RecQ helicase, Rqh1, plays a critical role in this process. This is demonstrated in {Delta}rqh1 cells that, following treatment with hydroxyurea (HU), undergo an aberrant mitosis leading to cell death. Previous data suggest that Rqh1 functions with homologous recombination (HR) in recovery from replication arrest. We have found that loss of the HR genes rhp55+ or rhp57+, but not rhp51+ or rhp54+, suppresses the HU sensitivity of {Delta}rqh1 cells. Much of this suppression requires Rhp51 and Rhp54. In addition, this suppression is partially dependent on swi5+. In budding yeast, overexpressing Rad51 (the Rhp51 homolog) minimized the need for Rad55/57 (Rhp55/57) in nucleoprotein filament formation. We overexpressed Rhp51 in Schizosaccharomyces pombe and found that it greatly reduced the requirement for Rhp55/57 in recovery from DNA damage. However, overexpressing Rhp51 did not change the {Delta}rhp55 suppression of the HU sensitivity of {Delta}rqh1, supporting an Rhp55/57 function during HR independent of nucleoprotein filament formation. These results are consistent with Rqh1 playing a role late in HR following replication arrest and provide evidence for a postsynaptic function for Rhp55/57.




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