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Originally published as Genetics Published Articles Ahead of Print on August 22, 2005.

Genetics, Vol. 172, 27-39, January 2006, Copyright © 2006
doi:10.1534/genetics.105.047845

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Evidence of Meiotic Crossover Control in Saccharomyces cerevisiae Through Mec1-Mediated Phosphorylation of Replication Protein A

Amy J. Bartrand, Dagmawi Iyasu, Suzanne M. Marinco and George S. Brush1

Barbara Ann Karmanos Cancer Institute and Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201

1 Corresponding author: Karmanos Cancer Institute, Program in Molecular Biology and Human Genetics, Wayne State University School of Medicine, 3114 Prentis Ctr., 110 E. Warren Ave., Detroit, MI 48201.
E-mail: brushg{at}karmanos.org

Replication protein A (RPA) is the major single-stranded DNA-binding protein in eukaryotes, essential for DNA replication, repair, and recombination. During mitosis and meiosis in budding yeast, RPA becomes phosphorylated in reactions that require the Mec1 protein kinase, a central checkpoint regulator and homolog of human ATR. Through mass spectrometry and site-directed mutagenesis, we have now identified a single serine residue in the middle subunit of the RPA heterotrimer that is targeted for phosphorylation by Mec1 both in vivo and in vitro. Cells containing a phosphomimetic version of RPA generated by mutation of this serine to aspartate exhibit a significant alteration in the pattern of meiotic crossovers for specific genetic intervals. These results suggest a new function of Mec1 that operates through RPA to locally control reciprocal recombination.




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[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the Genetics Society of America.