Loss of Cohesin Subunit Rec8 Switches Rad51 Mediator Dependence in Resistance to Formaldehyde Toxicity in .

TitleLoss of Cohesin Subunit Rec8 Switches Rad51 Mediator Dependence in Resistance to Formaldehyde Toxicity in .
Publication TypeJournal Article
Year of Publication2018
AuthorsSutherland JH, Holloman WK
Date Published2018 10
KeywordsCell Cycle Proteins, Chromosomal Proteins, Non-Histone, Drug Resistance, Fungal, Formaldehyde, Fungal Proteins, Homologous Recombination, Rad51 Recombinase, Rad52 DNA Repair and Recombination Protein, Ustilago

DNA-protein cross-links (DPCs) are frequently occurring lesions that provoke continual threats to the integrity of the genome by interference with replication and transcription. Reactive aldehydes generated from endogenous metabolic processes or produced in the environment are sources that trigger cross-linking of DNA with associated proteins. DNA repair pathways in place for removing DPCs, or for bypassing them to enable completion of replication, include homologous recombination (HR) and replication fork remodeling (FR) systems. Here, we surveyed a set of mutants defective in known HR and FR components to determine their contribution toward maintaining resistance to chronic formaldehyde (FA) exposure in , a fungus that relies on the BRCA2-family member Brh2 as the principal Rad51 mediator in repair of DNA strand breaks. We found that, in addition to Brh2, Rad52 was also vital for resistance to FA. Deleting the gene for Rec8, a kleisin subunit of cohesin, eliminated the requirement for Brh2, but not Rad52, in FA resistance. The Rad51 mutant variant that is able to bind DNA but unable to dissociate from it was able to support resistance to FA. These findings suggest a model for DPC repair and tolerance that features a specialized role for Rad52, enabling Rad51 to access DNA in its noncanonical capacity of replication fork protection rather than DNA strand transfer.

Alternate JournalGenetics
PubMed ID30082279
PubMed Central IDPMC6216591

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