Double-strand break repair can lead to high frequencies of deletions within short CAG/CTG trinucleotide repeats |
| |
Authors: | G.-F. Richard B. Dujon J. E. Haber |
| |
Affiliation: | (1) Rosenstiel Center and Department of Biology, MS029, Brandeis University, Waltham, MA 02454-9110, USA e-mail: haber@hydra.rose.brandeis.edu, Fax: +1-781-7362405, US;(2) Unité de Génétique Moléculaire des Levures, URA1300 CNRS and UFR927 Univ. P. M. Curie, Institut Pasteur, 25, rue du Dr Roux, F-75724 Paris Cedex 15, France, FR |
| |
Abstract: | Trinucleotide repeats undergo contractions and expansions in humans, leading in some cases to fatal neurological disorders. The mechanism responsible for these large size variations is unknown, but replication-slippage events are often suggested as a possible source of instability. We constructed a genetic screen that allowed us to detect spontaneous expansions/contractions of a short trinucleotide repeat in yeast. We show that deletion of RAD27, a gene involved in the processing of Okazaki fragments, increases the frequency of contractions tenfold. Repair of a chromosomal double-strand break (DSB) using a trinucleotide repeat-containing template induces rearrangements of the repeat with a frequency 60 times higher than the natural rate of instability of the same repeat. Our data suggest that both gene conversion and single-strand annealing are major sources of trinucleotide repeat rearrangements. Received: 8 January 1999 / Accepted: 17 March 1999 |
| |
Keywords: | Trinucleotide repeats Double-strand break repair Gene conversion Yeast |
本文献已被 SpringerLink 等数据库收录! |
|