A novel Aspergillus nidulans serine/threonine protein kinase gene that is transcriptionally regulated by camptothecin

Marcelo A. Vallim; Camile P. Semighini; Renata C. Pascon; Maria Helena S. Goldman & Gustavo H. Goldman

Author address: 

Universidade de São Paulo, Faculdade de Ciëncias Farmacëuticas de Ribeirão Preto. Av. do Café, S/N. 14040-903 - Ribeirão Preto-SP Brazil

Abstract: 

The DNA damage response is a protective mechanism that ensures the maintenance of genomic integrity during cellular reproduction. It consists of extensive repair systems that deal directly with DNA damage, as well as surveillance systems, known as checkpoints, which arrest the cell cycle and provide time for DNA repair before the critical events of replication and segregation occur. Camptothecin (CPT) is an anti-cancer drug that targets eukaryotic DNA topoisomerase I by trapping the covalent complex formed by this enzyme and DNA. Damage to DNA occurs when the replication fork encounters the ternary complex (DNA-topoisomerase I-camptothecin) causing double-strand break and in higher eukaryotes, apoptosis. The filamentous fungus Aspergillus nidulans is a biological model to study cell cycle control and DNA damage response, however the mechanism how it responds to double-strand breaks caused by CPT is unknown. In order to uncover genes that might be involved in providing the response to damage to DNA in this fungus, Differential Display Reverse Transcription PCR technique (DD-RTPCR) was employed. Using this method we describe the isolation and characterization of a gene that encodes a novel putative serine/threonine kinase (anpk). Quantitative real-time RT-PCR showed that the transcription of anpk fluctuates during an 8 hours period. However, when camptothecin is added to the medium the anpk transcription is repressed showing its lowest accumulation at 1 hour after CPT induction whereas at 8 hours the drug induced anpk transcription. These results suggest that this kinase might be involved in the mechanism by which A. nidulans responds to DNA damage. This project is sponsored by Fundaçí£o de Amparo a Pesquisa do Estado de Sí£o to M.A. Vallim (#00/01088-9)
2001

abstract No: 

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Full conference title: 

21st Fungal Genetics Conference
    • Fungal Genetics Conference 21st (2000)