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Molecular and Cellular Biology, December 2007, p. 8874-8885, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01095-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

S-Phase Checkpoint Pathways Stimulate the Mobility of the Retrovirus-Like Transposon Ty1{triangledown} ,{dagger}

M. Joan Curcio,1* Alison E. Kenny,1 Sharon Moore,2 David J. Garfinkel,2 Matthew Weintraub,1 Eric R. Gamache,1 and Derek T. Scholes1

Laboratory of Developmental Genetics, Wadsworth Center, Albany, New York 12201,1 Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, Frederick, Maryland 217022

Received 20 June 2007/ Returned for modification 24 July 2007/ Accepted 30 September 2007

The mobility of the Ty1 retrotransposon in the yeast Saccharomyces cerevisiae is restricted by a large collection of proteins that preserve the integrity of the genome during replication. Several of these repressors of Ty1 transposition (Rtt)/genome caretakers are orthologs of mammalian retroviral restriction factors. In rtt/genome caretaker mutants, levels of Ty1 cDNA and mobility are increased; however, the mechanisms underlying Ty1 hypermobility in most rtt mutants are poorly characterized. Here, we show that either or both of two S-phase checkpoint pathways, the replication stress pathway and the DNA damage pathway, partially or strongly stimulate Ty1 mobility in 19 rtt/genome caretaker mutants. In contrast, neither checkpoint pathway is required for Ty1 hypermobility in two rtt mutants that are competent for genome maintenance. In rtt101{Delta} mutants, hypermobility is stimulated through the DNA damage pathway components Rad9, Rad24, Mec1, Rad53, and Dun1 but not Chk1. We provide evidence that Ty1 cDNA is not the direct target of the DNA damage pathway in rtt101{Delta} mutants; instead, levels of Ty1 integrase and reverse transcriptase proteins, as well as reverse transcriptase activity, are significantly elevated. We propose that DNA lesions created in the absence of Rtt/genome caretakers trigger S-phase checkpoint pathways to stimulate Ty1 reverse transcriptase activity.

* Corresponding author. Mailing address: Center for Medical Sciences, Wadsworth Center, P.O. Box 2002, Albany, NY 12201-2002. Phone: (518) 473-6078. Fax: (518) 474-3181. E-mail: curcio{at}wadsworth.org

{triangledown} Published ahead of print on 8 October 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, December 2007, p. 8874-8885, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01095-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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