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Molecular and Cellular Biology, April 2006, p. 3098-3105, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3098-3105.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcription of a Donor Enhances Its Use during Double-Strand Break-Induced Gene Conversion in Human Cells

Ezra Schildkraut,{dagger} Cheryl A. Miller, and Jac A. Nickoloff*

Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131

Received 29 August 2005/ Returned for modification 11 November 2005/ Accepted 25 January 2006

Homologous recombination (HR) mediates accurate repair of double-strand breaks (DSBs) but carries the risk of large-scale genetic change, including loss of heterozygosity, deletions, inversions, and translocations. Nearly one-third of the human genome consists of repetitive sequences, and DSB repair by HR often requires choices among several homologous repair templates, including homologous chromosomes, sister chromatids, and linked or unlinked repeats. Donor preference during DSB-induced gene conversion was analyzed by using several HR substrates with three copies of neo targeted to a human chromosome. Repair of I-SceI nuclease-induced DSBs in one neo (the recipient) required a choice between two donor neo genes. When both donors were downstream, there was no significant bias for proximal or distal donors. When donors flanked the recipient, we observed a marked (85%) preference for the downstream donor. Reversing the HR substrate in the chromosome eliminated this preference, indicating that donor choice is influenced by factors extrinsic to the HR substrate. Prior indirect evidence suggested that transcription might increase donor use. We tested this question directly and found that increased transcription of a donor enhances its use during gene conversion. A preference for transcribed donors would minimize the use of nontranscribed (i.e., pseudogene) templates during repair and thus help maintain genome stability.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131. Phone: (505) 272-6960. Fax: (505) 272-6029. E-mail: jnickoloff{at}salud.unm.edu.

{dagger} Present address: CerroSci LLC, P.O. Box 177, Cerrillos, NM 87010.

Molecular and Cellular Biology, April 2006, p. 3098-3105, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3098-3105.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gottipati, P., Helleday, T. (2009). Transcription-associated recombination in eukaryotes: link between transcription, replication and recombination. Mutagenesis 24: 203-210 [Abstract] [Full Text]  


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