Aspergillus nidulans uvsB^ATR and scaA^NBS1 Genes Show Genetic Interactions during Recovery from Replication Stress and DNA Damage

Authors

Marcia Regina von Zeska Kress Fagundes, Universidade de Sao Paulo, Sao Paulo, Brazil
Camile P. Semighini, Universidade de Sao Paulo, Sao Paulo, Brazil
Iran Malazavi, Universidade de Sao Paulo, Sao Paulo, Brazil
Marcela Savoldi, Universidade de Sao Paulo, Sao Paulo, Brazil
Joel Fernandes de Lima, Universidade de Sao Paulo, Sao Paulo, Brazil
Maria Helena de Souza Goldman, Universidade de Sao Paulo, Sao Paulo, Brazil
Steven D. Harris, University of Nebraska-LincolnFollow
Gustavo Henrique Goldman, Universidade de Sao Paulo, Sao Paulo, Brazil

Document Type

Article

Date of this Version

July 2005

Comments

Published in EUKARYOTIC CELL, July 2005, p. 1239–1252 Vol. 4, No. 7. Copyright © 2005, American Society for Microbiology. Used by permission.

Abstract

The ATM/ATR kinases and the Mre11 (Mre11-Rad50-Nbs1) protein complex are central players in the cellular DNA damage response. Here we characterize possible interactions between Aspergillus nidulans uvsB- ^ATR and the Mre11 complex (scaA^NBS1). We demonstrate that there is an epistatic relationship between uvsB^ATR, the homolog of the ATR/MEC1 gene, and scaA^NBSI, the homolog of the NBS1/XRS2 gene, for both repair and checkpoint functions and that correct ScaA^NBS1 expression during recovery from replication stress depends on uvsB^ATR. In addition, we also show that the formation of UvsC foci during recovery from replication stress is dependent on both uvsB^ATR and scaA^NBS1 function. Furthermore, ScaA^NBS1 is also dependent on uvsB^ATR for nuclear focus formation upon the induction of DNA double-strand breaks by phleomycin. Our results highlight the extensive genetic interactions between UvsB and the Mre11 complex that are required for S-phase progression and recovery from DNA damage.