Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis
Abstract
Cells maintain a small arsenal of resolving functions to process and eliminate complex DNA intermediates that result as a consequence of homologous recombination and distressed replication. Ordinarily the homologous recombination system serves as a high-fidelity mechanism to restore the integrity of a damaged genome, but in the absence of the appropriate resolving function it can turn DNA intermediates resulting from replication stress into pathological forms that are toxic to cells. Here we have investigated how the nucleases Mus81 and Gen1 and the helicase Blm contribute to survival after DNA damage or replication stress in Ustilago maydis cells with crippled yet homologous recombination-proficient forms of Brh2, the BRCA2 ortholog and primary Rad51 mediator. We found collaboration among the factors. Notable were three findings. First, the ability of Gen1 to rescue hydroxyurea sensitivity of dysfunctional Blm requires the absence of Mus81. Second, the response of mutants defective in... Blm and Gen1 to hydroxyurea challenge is markedly similar suggesting cooperation of these factors in the same pathway. Third, the repair proficiency of Brh2 mutant variants deleted of its N-terminal DNA binding region requires not only Rad52 but also Gen1. and Mus81. We suggest these factors comprise a sub pathway for channeling repair when Brh2 is compromised in its interplay with DNA.
Keywords:
Replication stress / Mus81 / Gen1 / DNA repair / BRCA2 / BlmSource:
DNA Repair, 2018, 63, 47-55Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- National Institutes of Health [GM079859]
- The Role of Transcription Factors and Small RNAs in Abiotic Stress Response in Plants and Genetic Diversity of Plant Species Important for Agriculture and Biotechnology (RS-MESTD-Basic Research (BR or ON)-173005)
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM079859] Funding Source: NIH RePORTER
Note:
- Peer-reviewed manuscript: https://imagine.imgge.bg.ac.rs/handle/123456789/1626
Related info:
DOI: 10.1016/j.dnarep.2018.01.010
ISSN: 1568-7864
PubMed: 29414053
WoS: 000427341600006
Scopus: 2-s2.0-85041416371
Collections
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kojić, Milorad AU - Milisavljević, Mira AU - Holloman, William K. PY - 2018 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1190 AB - Cells maintain a small arsenal of resolving functions to process and eliminate complex DNA intermediates that result as a consequence of homologous recombination and distressed replication. Ordinarily the homologous recombination system serves as a high-fidelity mechanism to restore the integrity of a damaged genome, but in the absence of the appropriate resolving function it can turn DNA intermediates resulting from replication stress into pathological forms that are toxic to cells. Here we have investigated how the nucleases Mus81 and Gen1 and the helicase Blm contribute to survival after DNA damage or replication stress in Ustilago maydis cells with crippled yet homologous recombination-proficient forms of Brh2, the BRCA2 ortholog and primary Rad51 mediator. We found collaboration among the factors. Notable were three findings. First, the ability of Gen1 to rescue hydroxyurea sensitivity of dysfunctional Blm requires the absence of Mus81. Second, the response of mutants defective in Blm and Gen1 to hydroxyurea challenge is markedly similar suggesting cooperation of these factors in the same pathway. Third, the repair proficiency of Brh2 mutant variants deleted of its N-terminal DNA binding region requires not only Rad52 but also Gen1. and Mus81. We suggest these factors comprise a sub pathway for channeling repair when Brh2 is compromised in its interplay with DNA. PB - Elsevier Science Bv, Amsterdam T2 - DNA Repair T1 - Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis EP - 55 SP - 47 VL - 63 DO - 10.1016/j.dnarep.2018.01.010 ER -
@article{ author = "Kojić, Milorad and Milisavljević, Mira and Holloman, William K.", year = "2018", abstract = "Cells maintain a small arsenal of resolving functions to process and eliminate complex DNA intermediates that result as a consequence of homologous recombination and distressed replication. Ordinarily the homologous recombination system serves as a high-fidelity mechanism to restore the integrity of a damaged genome, but in the absence of the appropriate resolving function it can turn DNA intermediates resulting from replication stress into pathological forms that are toxic to cells. Here we have investigated how the nucleases Mus81 and Gen1 and the helicase Blm contribute to survival after DNA damage or replication stress in Ustilago maydis cells with crippled yet homologous recombination-proficient forms of Brh2, the BRCA2 ortholog and primary Rad51 mediator. We found collaboration among the factors. Notable were three findings. First, the ability of Gen1 to rescue hydroxyurea sensitivity of dysfunctional Blm requires the absence of Mus81. Second, the response of mutants defective in Blm and Gen1 to hydroxyurea challenge is markedly similar suggesting cooperation of these factors in the same pathway. Third, the repair proficiency of Brh2 mutant variants deleted of its N-terminal DNA binding region requires not only Rad52 but also Gen1. and Mus81. We suggest these factors comprise a sub pathway for channeling repair when Brh2 is compromised in its interplay with DNA.", publisher = "Elsevier Science Bv, Amsterdam", journal = "DNA Repair", title = "Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis", pages = "55-47", volume = "63", doi = "10.1016/j.dnarep.2018.01.010" }
Kojić, M., Milisavljević, M.,& Holloman, W. K.. (2018). Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis. in DNA Repair Elsevier Science Bv, Amsterdam., 63, 47-55. https://doi.org/10.1016/j.dnarep.2018.01.010
Kojić M, Milisavljević M, Holloman WK. Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis. in DNA Repair. 2018;63:47-55. doi:10.1016/j.dnarep.2018.01.010 .
Kojić, Milorad, Milisavljević, Mira, Holloman, William K., "Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis" in DNA Repair, 63 (2018):47-55, https://doi.org/10.1016/j.dnarep.2018.01.010 . .