Aspergillus nidulans rad50 gene inactivation leads to hypersensitivity to DNA damaging agents, and sexual and cell cycle checkpoint defects.

Iran Malavazi1, Joel Fernandes Lima1, Márcia Regina von Zeska Kress Fagundes1, Vladimir P. Efimov2, Maria Helena de Souza Goldman3 and Gustavo Henrique Goldman1.

Author address: 

1Faculdade de Ciëncias Farmacëuticas de Ribeirão Preto and 3Faculdade de Filosofia, Ciëncias e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil. 2Department of Pharmacology, University of Medicine and Dentistry of New Jersey, US

Abstract: 

The hMRE11-hRAD50-NBS1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA-damage detection to DNA-repair and cell cycle-checkpoint functions. We have identified A. nidulans rad50 mutant in a screen for dynein synthetic lethals. The rad50 gene was cloned by complementation of the sporulation deficiency phenotype of this mutant. A transversion G-C at the position 2509 (Ala-692-Pro amino acid change) in the rad50 mutant causes sensitivity to several DNA damaging agents. This mutation is novel and occurs at the coiled-coil region of the Rad50. We have deleted part of the coiled-coil region and few aminoacids of the Rad50-Mre11 interaction region and assessed several phenotypic traits in this deletion strain. Besides sensitivity to several DNA damaging agents, this deletion strain is also impaired in the intra-S-phase and DNA replication checkpoints. There is a genetic interaction between rad50 and bimEAPC1 at both S-phase checkpoints. Interestingly, we have also seen epistasis between rad50 and uvsBATR when germinating conidia of the corresponding double mutant are exposed to ultraviolet light. In addition, the rad50 gene is also important for ascospore viability. Financial support: FAPESP and CNPq, Brazil
2005

abstract No: 

583

Full conference title: 

23rd Fungal Genetics Conference
    • Fungal Genetics Conference 23rd (2002)