Title

The role of SepB in the maintenance of genome stability in Aspergillus nidulans

Date of Completion

January 2003

Keywords

Biology, Molecular|Biology, Genetics|Biology, Microbiology

Degree

Ph.D.

Abstract

SepB is an essential protein required for chromosomal DNA metabolism in Aspergillus nidulans. SepB is a member of a conserved family of proteins that includes homologs in yeast (Ctf4p) and humans (hAND-1). A characteristic feature of these proteins is the presence of multiple protein-protein interaction domains, which suggests that they may function as molecular scaffolds. We provide evidence that SepB functions in the repair of DNA double strand breaks (DSBs) via the homologous recombination pathway, as demonstrated by the genetic interactions with uvsC (RAD51), musN (RECQ/BLM), and uvsB (ATR) and the sepB3 sensitivity to agents that cause DSBs. We also provide evidence that the loss of SepB function disrupts the formation of DNA damage induced UvsC (RAD51) nuclear foci, the proposed site of active DNA repair. We propose that SepB/AND-1 protein family members facilitate the formation of a multimeric protein complex that functions in DNA replication and homologous recombination. Moreover, our results suggest that SepB/AND-1 dysfunction can genetically modify the mutant phenotypes caused by mutations affecting RecQ/BLM or Mec1p/ATR. ^