Collaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis.

TitleCollaboration in the actions of Brh2 with resolving functions during DNA repair and replication stress in Ustilago maydis.
Publication TypeJournal Article
Year of Publication2018
AuthorsKojic M, Milisavljevic M, Holloman WK
JournalDNA Repair (Amst)
Date Published2018 03
KeywordsBRCA2 Protein, DNA, DNA Replication, Endonucleases, Fungal Proteins, Holliday Junction Resolvases, Hydroxyurea, Mutagens, Rad51 Recombinase, Recombinational DNA Repair, RecQ Helicases, Ustilago

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 subpathway for channeling repair when Brh2 is compromised in its interplay with DNA.

Alternate JournalDNA Repair (Amst)
PubMed ID29414053
PubMed Central IDPMC5826808
Grant ListR01 GM079859 / GM / NIGMS NIH HHS / United States

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