Send to

Choose Destination
Genetics. 2018 Oct;210(2):559-572. doi: 10.1534/genetics.118.301439. Epub 2018 Aug 6.

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

Author information

Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065.
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065


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 Ustilago maydis, 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 Rad51K133R 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.


DNA repair; DNA-protein cross-links; Rad52; Rec8; fork remodeling; formaldehyde toxicity

[Available on 2019-10-01]
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center