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Rôle de protéines de la réparation des cassures double brin dans l'homéostasie télomérique chez Arabidopsis thaliana

Abstract : Telomeres are the specialised nucleoprotein structures evolved to avoid progressive replicative shortening and recombinational instability of the ends of linear chromosomes. Notwithstanding this role of telomeres in "hiding" chromosome ends from DNA repair and recombination, many repair and recombination proteins play essential roles in telomere function and chromosome stability. Among these are RAD50 from MRE11/RAD50/XRS2(NBS1) complex and XPF/ERCC1 structure-specific endonuclease; both known for their essential role in DNA repair pathways and the subject of considerable interest in studies of recombination. We identified two roles for the RAD50 protein in telomere maintenance and the protection of chromosome ends both in the presence and absence of telomerase. Absence of AtRAD50 significantly increases chromosomal fusions involving shortened telomeres. We proposed that this protective role of RAD50 protein on shortened telomeres results from its action in constraining recombination to sister chromatids and thus avoiding end-to-end interactions. We have research the mechanisms involved in chromosomal fusions in atrad50 mutants by crosses between ATRAD50 and different NHEJ or HR DNA repair mutants. In contrast to the situation in mammalian cells, we observe no chromosomal instability in the corresponding plants mutated for either XPF (AtRAD1) or ERCC1 (AtERCC1) orthologs. However in the absence of telomerase, mutation of either of these two genes induces a significantly earlier onset of chromosomal instability without general acceleration of telomeric repeat loss, but associated with the presence of cytologically visible extrachromosomal DNA fragments. Extensive FISH analyses show that these DNAs are broken chromosomes from two specific chromosome arms. Our data thus indicate a protective role of RAD1/ERCC1 against 3' Gstrand overhang invasion of interstitial telomeric repeats. The fact that the rad1 (or ercc1) mutants dramatically potentiate levels of chromosome instability in telomerase mutants has important implications for models of the roles of recombination at telomeres.
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https://theses.hal.science/tel-00725958
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Submitted on : Tuesday, August 28, 2012 - 2:19:12 PM
Last modification on : Tuesday, April 20, 2021 - 11:22:02 AM
Long-term archiving on: : Thursday, November 29, 2012 - 3:36:13 AM

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  • HAL Id : tel-00725958, version 1

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Jean-Baptiste Vannier. Rôle de protéines de la réparation des cassures double brin dans l'homéostasie télomérique chez Arabidopsis thaliana. Génétique. Université Blaise Pascal - Clermont-Ferrand II, 2009. Français. ⟨NNT : 2009CLF21911⟩. ⟨tel-00725958⟩

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