Meiotic instability of human minisatellite CEB1 in yeast requires DNA double-strand breaks.

Abstract : Minisatellites are tandemly repeated DNA sequences of 10-100-bp units. Some minisatellite loci are highly unstable in the human germ line, and structural analysis of mutant alleles has suggested that repeat instability results from a recombination-based process. To provide insights into the molecular mechanism of human minisatellite instability, we developed Saccharomyces cerevisiae strains carrying alleles of the most unstable human minisatellite locus, CEB1 (ref. 2). We observed that CEB1 is destabilized in meiosis, resulting in a variety of intra- and inter-allelic gains or losses of repeat units, similar to rearrangements described in humans. Using mutations affecting the initiation of recombination (spo11) or mismatch repair (msh2 pms1 ), we demonstrate that meiotic destabilization depends on the initiation of homologous recombination at nearby DNA double-strand break (DSBs) sites and involves a 'rearranged heteroduplex' intermediate. Most of the human and yeast data can be explained and unified in the context of DSB repair models.
Type de document :
Article dans une revue
Nature Genetics, Nature Publishing Group, 1999, 23 (3), pp.367-71
Liste complète des métadonnées

https://hal-ensta.archives-ouvertes.fr/hal-01159817
Contributeur : Gilles Vergnaud <>
Soumis le : mercredi 3 juin 2015 - 18:53:56
Dernière modification le : jeudi 11 janvier 2018 - 06:19:24

Identifiants

  • HAL Id : hal-01159817, version 1
  • PUBMED : 10545956

Collections

Citation

H Debrauwère, J Buard, J Tessier, D Aubert, Gilles Vergnaud, et al.. Meiotic instability of human minisatellite CEB1 in yeast requires DNA double-strand breaks.. Nature Genetics, Nature Publishing Group, 1999, 23 (3), pp.367-71. 〈hal-01159817〉

Partager

Métriques

Consultations de la notice

83