Different roles of the Mre11 complex in the DNA damage response in Aspergillus nidulans

Summary The Mre11‐Rad50‐Nbs1 protein complex has emerged as a central player in the cellular DNA damage response. Mutations in scaANBS1, which encodes the apparent homologue of human Nbs1 in Aspergillus nidulans, inhibit growth in the presence of the anti‐topoisomerase I drug camptothecin. We have u...

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Bibliographic Details
Published in:Molecular microbiology 2003-06, Vol.48 (6), p.1693-1709
Main Authors: Semighini, Camile P., Von Zeska Kress Fagundes, Márcia Regina, Ferreira, Joseane Cristina, Pascon, Renata Castiglioni, De Souza Goldman, Maria Helena, Goldman, Gustavo Henrique
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Aspergillus nidulans - genetics
Aspergillus nidulans - metabolism
Aspergillus nidulans - physiology
Base Sequence
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
DNA Damage
DNA Repair
DNA, Complementary - genetics
DNA, Fungal
DNA-Binding Proteins - metabolism
Endodeoxyribonucleases - metabolism
Exodeoxyribonucleases - metabolism
Fungal Proteins - genetics
Fungal Proteins - metabolism
Humans
Molecular Sequence Data
Mutation
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Saccharomyces cerevisiae Proteins - metabolism
Two-Hybrid System Techniques
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Summary:Summary The Mre11‐Rad50‐Nbs1 protein complex has emerged as a central player in the cellular DNA damage response. Mutations in scaANBS1, which encodes the apparent homologue of human Nbs1 in Aspergillus nidulans, inhibit growth in the presence of the anti‐topoisomerase I drug camptothecin. We have used the scaANBS1 cDNA as a bait in a yeast two‐hybrid screening and report the identification of the A. nidulans Mre11 homologue (mreA). The inactivated mreA strain was more sensitive to several DNA damaging and oxidative stress agents. Septation in A. nidulans is dependent not only on the uvsBATR gene, but also on the mre11 complex. scaANBS1 and mreA genes are both involved in the DNA replication checkpoint whereas mreA is specifically involved in the intra‐S‐phase checkpoint. ScaANBS1 also participates in G2‐M checkpoint control upon DNA damage caused by MMS. In addition, the scaANBS1 gene is also important for ascospore viability, whereas mreA is required for successful meiosis in A. nidulans. Consistent with this view, the Mre11 complex and the uvsCRAD51 gene are highly expressed at the mRNA level during the sexual development.
ISSN:0950-382X
1365-2958
DOI:10.1046/j.1365-2958.2003.03539.x