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Separable roles for exonuclease I in meiotic DNA double-strand break repair

By Rebecca E. Keelagher, Victoria E. Cotton, Alastair S. H. Goldman and Rhona H. Borts

Abstract

Exo1 is a member of the Rad2 protein family and possesses both 5' –3' exonuclease and 5 flap endonuclease\ud activities. In addition to performing a variety of functions during mitotic growth, Exo1 is also\ud important for the production of crossovers during meiosis. However, its precise molecular role has\ud remained ambiguous and several models have been proposed to account for the crossover deficit observed\ud in its absence. Here, we present physical evidence that the nuclease activity of Exo1 is essential for normal\ud 5' –3' resection at the Spo11-dependent HIS4 hotspot in otherwise wild-type cells. This same activity\ud was also required for normal levels of gene conversion at the locus. However, gene conversions were\ud frequently observed at a distance beyond that at which resection was readily detectable arguing that it\ud is not the extent of the initial DNA end resection that limits heteroduplex formation. In addition to these\ud nuclease-dependent functions, we found that an exo1-D173A mutant defective in nuclease activity is able\ud to maintain crossing-over at wild-type levels in a number of genetic intervals, suggesting that Exo1 also\ud plays a nuclease-independent role in crossover promotion

Topics: EXO1, Meiosis, Recombination, Resection, Double-strand break
Publisher: Elsevier
Year: 2010
DOI identifier: 10.1016/j.dnarep.2010.09.024
OAI identifier: oai:lra.le.ac.uk:2381/8936
Journal:

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