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Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress.

TitleBrh2 domain function distinguished by differential cellular responses to DNA damage and replication stress.
Publication TypeJournal Article
Year of Publication2012
AuthorsKojic M, Holloman WK
JournalMol Microbiol
Volume83
Issue2
Pagination351-61
Date Published2012 Jan
ISSN1365-2958
KeywordsDNA, DNA Damage, DNA Repair, DNA Replication, DNA-Binding Proteins, Hydroxyurea, Protein Binding, Protein Structure, Tertiary, Recombination, Genetic, Stress, Physiological, Transcription Factors, Ustilago
Abstract

Mutants of the fungus Ustilago maydis defective in the RecQ helicase Blm are highly sensitive to killing by the DNA replication stressor hydroxyurea. This sensitivity or toxicity is dependent on the homologous recombination (HR) system and apparently results from formation of dead-end HR DNA intermediates. HU toxicity can be suppressed by deletion of the gene encoding Brh2, the BRCA2 orthologue that serves to regulate HR by mediating Rad51 filament formation on single-stranded DNA. Brh2 harbours two different DNA-binding domains that contribute to HR function. DNA-binding activity from a single domain is sufficient to provide Brh2 functional activity in HR, but to enable HU-induced killing two functional DNA-binding domains must be present. Despite this stringent requirement for dual functioning domains, the source of DNA-binding domains is less critical in that heterologous domains can substitute for the native endogenous ones. The results suggest a model in which the nature of the DNA lesion is an important determinant in the functional response of Brh2 action.

DOI10.1111/j.1365-2958.2011.07935.x
Alternate JournalMol. Microbiol.
PubMed ID22171788
PubMed Central IDPMC3256287
Grant ListGM042482 / GM / NIGMS NIH HHS / United States
GM079859 / GM / NIGMS NIH HHS / United States
R01 GM042482-20 / GM / NIGMS NIH HHS / United States
R01 GM042482-21 / GM / NIGMS NIH HHS / United States
R01 GM079859-06 / GM / NIGMS NIH HHS / United States

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