A study of the DNA damage checkpoint in Candida albicans: uncoupling of the functions of Rad53 in DNA repair, cell cycle regulation and genotoxic stress-induced polarized growth.

Abstract : In response to genotoxic stress (GS), Candida albicans can undergo polarized growth and massive genome rearrangements including loss-of-heterozygosity (LOH) events. We evaluated the contribution of the CaRad53p and CaDun1p kinases of the DNA damage checkpoint (DDCP) in these processes. Characterization of C. albicans rad53ΔΔ and dun1ΔΔ mutants revealed that the two kinases were involved in the maintenance of heterozygosity. SNP-RFLP typing and whole-genome sequencing of rad53ΔΔ isolates having undergone a LOH revealed that, according to the chromosome on which LOH had occurred, these were predominantly due to break-induced replication/mitotic cross-over or chromosome loss. Loss of CaRAD53 also resulted in frequent aneuploidies. Deletion of CaDUN1 led to an increase in recombination-dependent LOH but did not trigger aneuploidies. It also increased GS sensitivity but did not impair GS-induced polarized growth contrary to CaRAD53 deletion. Characterization of CaRad53p site-directed mutants demonstrated that its kinase activity and N-terminal phosphorylation sites were crucial for its function in the resistance to GS, maintenance of heterozygosity, cell cycle regulation and polarized growth. Moreover, using phosphomimic mutants, we revealed an uncoupling of the functions of CaRad53p in these different processes, thus providing a novel understanding of how the DDCP may regulate downstream events in response to GS.
Type de document :
Article dans une revue
Molecular Microbiology, Wiley, 2013, 91 (3), pp.452-71. 〈10.1111/mmi.12471〉
Liste complète des métadonnées

Littérature citée [54 références]  Voir  Masquer  Télécharger

https://hal-pasteur.archives-ouvertes.fr/pasteur-01522639
Contributeur : Christelle Lenormand <>
Soumis le : lundi 15 mai 2017 - 12:21:21
Dernière modification le : jeudi 15 novembre 2018 - 20:27:44
Document(s) archivé(s) le : jeudi 17 août 2017 - 00:40:00

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Collections

Citation

Raphaël Loll-Krippleber, Christophe D'Enfert, Adeline Feri, Dorothée Diogo, Aurélie Perin, et al.. A study of the DNA damage checkpoint in Candida albicans: uncoupling of the functions of Rad53 in DNA repair, cell cycle regulation and genotoxic stress-induced polarized growth.. Molecular Microbiology, Wiley, 2013, 91 (3), pp.452-71. 〈10.1111/mmi.12471〉. 〈pasteur-01522639〉

Partager

Métriques

Consultations de la notice

94