Arthralgia plus postitive treatment of rheumatoid arthritis - No [Arthralgien plus positive ACPA - pr?emptive Therapie der rheumatoiden Arthritis? Contra]

摘要

Brh2, the BRCA2 ortholog in the fungus Ustilago maydis, harbors two different DNA-binding domains, one located in the N-terminal region and the other located in the C-terminal region. Here we were interested in comparing the biochemical properties of Brh2 fragments, Brh2NT and Brh2CT, respectively, harboring the two different DNA-binding regions to understand the mechanistic purpose of dual DNA-interaction domains. With oligonucleotide substrates to model different DNA conformations, it was found that the substrate specificity of Brh2NT and Brh2CT was almost indistinguishable although avidity was different depending on salt concentration. DNA annealing activity inherent in Brh2 was found to be attributable to Brh2NT. Likewise, activity responsible for a second-end capture reaction modeling a later step in repair of DNA double-strand breaks was found attributable to Brh2NT. Efficient annealing of DNA strands coated with RPA required full length Brh2 rather than Brh2NT suggesting Brh2CT contributes to the activity when RPA is present. Brh2NT and Brh2CT were both found capable of physically interacting with RPA. The results suggest that while the two DNA-binding regions of Brh2 appear functionally redundant in certain aspects of DNA repair, they differ in fundamental properties, and likely contribute in different ways to repair processes involving or arising from stalled DNA replication forks.