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Molecular and Cellular Biology, March 2009, p. 1432-1441, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01469-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Aberrant Double-Strand Break Repair Resulting in Half Crossovers in Mutants Defective for Rad51 or the DNA Polymerase {delta} Complex{triangledown}

Catherine E. Smith,1,2,{dagger} Alicia F. Lam,1 and Lorraine S. Symington1*

Department of Microbiology,1 Graduate Program in Biology, Columbia University College of Physicians & Surgeons, New York, New York 100322

Received 18 September 2008/ Returned for modification 7 November 2008/ Accepted 1 January 2009

Homologous recombination is an error-free mechanism for the repair of DNA double-strand breaks (DSBs). Most DSB repair events occur by gene conversion limiting loss of heterozygosity (LOH) for markers downstream of the site of repair and restricting deleterious chromosome rearrangements. DSBs with only one end available for repair undergo strand invasion into a homologous duplex DNA, followed by replication to the chromosome end (break-induced replication [BIR]), leading to LOH for all markers downstream of the site of strand invasion. Using a transformation-based assay system, we show that most of the apparent BIR events that arise in diploid Saccharomyces cerevisiae rad51{Delta} mutants are due to half crossovers instead of BIR. These events lead to extensive LOH because one arm of chromosome III is deleted. This outcome is also observed in pol32{Delta} and pol3-ct mutants, defective for components of the DNA polymerase {delta} (Pol {delta}) complex. The half crossovers formed in Pol {delta} complex mutants show evidence of limited homology-dependent DNA synthesis and are partially Mus81 dependent, suggesting that strand invasion occurs and the stalled intermediate is subsequently cleaved. In contrast to rad51{Delta} mutants, the Pol {delta} complex mutants are proficient for repair of a 238-bp gap by gene conversion. Thus, the BIR defect observed for rad51 mutants is due to strand invasion failure, whereas the Pol {delta} complex mutants are proficient for strand invasion but unable to complete extensive tracts of recombination-initiated DNA synthesis.

* Corresponding author. Mailing address: Columbia University Medical Center, Department of Microbiology, 701 W. 168th St., Rm. 916, New York, NY 10032-2704. Phone: (212) 305-4793. Fax: (212) 305-1741. E-mail: lss5{at}columbia.edu

{triangledown} Published ahead of print on 12 January 2009.

{dagger} Present address: Ludwig Institute for Cancer Research, UCSD School of Medicine, La Jolla, CA 92130.

Molecular and Cellular Biology, March 2009, p. 1432-1441, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01469-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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