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Molecular and Cellular Biology, November 2005, p. 9221-9231, Vol. 25, No. 21
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.21.9221-9231.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Novel PMS1 Alleles Preferentially Affect the Repair of Primer Strand Loops during DNA Replication

Naz Erdeniz,¹ Sandra Dudley,¹ Regan Gealy,² Sue Jinks-Robertson,² and R. Michael Liskay^1*

Molecular and Medical Genetics, Oregon Health and Science University, L103, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239,¹ Department of Biology, Emory University, 1510 Clifton Rd., Atlanta, Georgia 30322²

Received 14 March 2005/ Returned for modification 11 April 2005/ Accepted 21 July 2005

Null mutations in DNA mismatch repair (MMR) genes elevate both base substitutions and insertions/deletions in simple sequence repeats. Data suggest that during replication of simple repeat sequences, polymerase slippage can generate single-strand loops on either the primer or template strand that are subsequently processed by the MMR machinery to prevent insertions and deletions, respectively. In the budding yeast Saccharomyces cerevisiae and mammalian cells, MMR appears to be more efficient at repairing mispairs comprised of loops on the template strand compared to loops on the primer strand. We identified two novel yeast pms1 alleles, pms1-G882E and pms1-H888R, which confer a strong defect in the repair of "primer strand" loops, while maintaining efficient repair of "template strand" loops. Furthermore, these alleles appear to affect equally the repair of 1-nucleotide primer strand loops during both leading- and lagging-strand replication. Interestingly, both pms1 mutants are proficient in the repair of 1-nucleotide loop mispairs in heteroduplex DNA generated during meiotic recombination. Our results suggest that the inherent inefficiency of primer strand loop repair is not simply a mismatch recognition problem but also involves Pms1 and other proteins that are presumed to function downstream of mismatch recognition, such as Mlh1. In addition, the findings reinforce the current view that during mutation avoidance, MMR is associated with the replication apparatus.

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* Corresponding author. Mailing address: Molecular and Medical Genetics, Oregon Health and Science University, L103, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098. Phone: (503) 494-3475. Fax: (503) 494-6886. E-mail: liskaym{at}ohsu.edu.

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Molecular and Cellular Biology, November 2005, p. 9221-9231, Vol. 25, No. 21
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.21.9221-9231.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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