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Molecular and Cellular Biology, April 2000, p. 2436-2445, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Nucleotide Excision Repair/TFIIH Helicases Rad3 and Ssl2 Inhibit Short-Sequence Recombination and Ty1 Retrotransposition by Similar Mechanisms

Bum-Soo Lee,1 Liu Bi,2 David J. Garfinkel,1,* and Adam M. Bailis2

Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201,1 and Department of Molecular Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 910102

Received 20 October 1999/Returned for modification 22 December 1999/Accepted 14 January 2000

Eukaryotic genomes contain potentially unstable sequences whose rearrangement threatens genome structure and function. Here we show that certain mutant alleles of the nucleotide excision repair (NER)/TFIIH helicase genes RAD3 and SSL2 (RAD25) confer synthetic lethality and destabilize the Saccharomyces cerevisiae genome by increasing both short-sequence recombination and Ty1 retrotransposition. The rad3-G595R and ssl2-rtt mutations do not markedly alter Ty1 RNA or protein levels or target site specificity. However, these mutations cause an increase in the physical stability of broken DNA molecules and unincorporated Ty1 cDNA, which leads to higher levels of short-sequence recombination and Ty1 retrotransposition. Our results link components of the core NER/TFIIH complex with genome stability, homologous recombination, and host defense against Ty1 retrotransposition via a mechanism that involves DNA degradation.

* Corresponding author. Mailing address: Gene Regulation and Chromosome Biology Laboratory, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, MD 21702-1201. Phone: (301) 846-5604. Fax: (301) 846-6911. E-mail: garfinke{at}ncifcrf.gov.

Molecular and Cellular Biology, April 2000, p. 2436-2445, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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