Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress
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 DN...A lesion is an important determinant in the functional response of Brh2 action.
Source:
Molecular Microbiology, 2012, 83, 2, 351-361Publisher:
- Wiley, Hoboken
Funding / projects:
- NIH [GM042482, GM079859]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM079859, R01GM042482] Funding Source: NIH RePORTER
Note:
- Peer-reviewed manuscript: https://imagine.imgge.bg.ac.rs/handle/123456789/1621
Related info:
DOI: 10.1111/j.1365-2958.2011.07935.x
ISSN: 0950-382X
PubMed: 22171788
WoS: 000298988600009
Scopus: 2-s2.0-84855764456
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Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kojić, Milorad AU - Holloman, William K. PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/584 AB - 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. PB - Wiley, Hoboken T2 - Molecular Microbiology T1 - Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress EP - 361 IS - 2 SP - 351 VL - 83 DO - 10.1111/j.1365-2958.2011.07935.x ER -
@article{ author = "Kojić, Milorad and Holloman, William K.", year = "2012", 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.", publisher = "Wiley, Hoboken", journal = "Molecular Microbiology", title = "Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress", pages = "361-351", number = "2", volume = "83", doi = "10.1111/j.1365-2958.2011.07935.x" }
Kojić, M.,& Holloman, W. K.. (2012). Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress. in Molecular Microbiology Wiley, Hoboken., 83(2), 351-361. https://doi.org/10.1111/j.1365-2958.2011.07935.x
Kojić M, Holloman WK. Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress. in Molecular Microbiology. 2012;83(2):351-361. doi:10.1111/j.1365-2958.2011.07935.x .
Kojić, Milorad, Holloman, William K., "Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress" in Molecular Microbiology, 83, no. 2 (2012):351-361, https://doi.org/10.1111/j.1365-2958.2011.07935.x . .