DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs

Barbora Stefanovie; Sarah R Hengel; Jarmila Mlcouskova; Jana Prochazkova; Mario Spirek; Fedor Nikulenkov; Daniel Nemecek; Brandon G Koch; Fletcher E Bain; Liping Yu; Maria Spies; Lumir Krejci

doi:10.1093/nar/gkz1052

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DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs

Journal article

Open access

Peer reviewed

DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs

Barbora Stefanovie, Sarah R Hengel, Jarmila Mlcouskova, Jana Prochazkova, Mario Spirek, Fedor Nikulenkov, Daniel Nemecek, Brandon G Koch, Fletcher E Bain, Liping Yu, …

Nucleic acids research, Vol.48(2), pp.694-708

01/24/2020

DOI: 10.1093/nar/gkz1052

PMCID: PMC6954417

PMID: 31799622

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Abstract

The proper repair of deleterious DNA lesions such as double strand breaks prevents genomic instability and carcinogenesis. In yeast, the Rad52 protein mediates DSB repair via homologous recombination. In mammalian cells, despite the presence of the RAD52 protein, the tumour suppressor protein BRCA2 acts as the predominant mediator during homologous recombination. For decades, it has been believed that the RAD52 protein played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (SSA). Recent studies have identified several new functions of the RAD52 protein and have drawn attention to its important role in genome maintenance. Here, we show that RAD52 activities are enhanced by interacting with a small and highly acidic protein called DSS1. Binding of DSS1 to RAD52 changes the RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates SSA activity and promotes strand invasion. Our work introduces for the first time RAD52 as another interacting partner of DSS1 and shows that both proteins are important players in the SSA and BIR pathways of DSB repair.

BRCA2 Protein - genetics

Carcinogenesis - genetics

DNA Breaks, Double-Stranded

DNA Repair - genetics

DNA-Binding Proteins - genetics

Genome, Human - genetics

Genomic Instability - genetics

Homologous Recombination - genetics

Humans

Osteosarcoma - genetics

Osteosarcoma - pathology

Proteasome Endopeptidase Complex - genetics

Protein Binding

Rad52 DNA Repair and Recombination Protein - genetics

Saccharomyces cerevisiae - genetics

Saccharomyces cerevisiae Proteins - genetics

Details

Title: Subtitle: DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs
Creators: Barbora Stefanovie - Masaryk University
Sarah R Hengel - University of Iowa
Jarmila Mlcouskova - Masaryk University
Jana Prochazkova - International Clinical Research Center, St. Anne's University Hospital in Brno, 62500 Brno, Czech Republic.
Mario Spirek - Masaryk University
Fedor Nikulenkov - International Clinical Research Center, St. Anne's University Hospital in Brno, 62500 Brno, Czech Republic.
Daniel Nemecek - Masaryk University
Brandon G Koch - University of Iowa
Fletcher E Bain - University of Iowa
Liping Yu - University of Iowa
Maria Spies - University of Iowa
Lumir Krejci - Masaryk University
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.48(2), pp.694-708
DOI: 10.1093/nar/gkz1052
PMID: 31799622
PMCID: PMC6954417
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Grant note: R01 CA232425 / NCI NIH HHS
Language: English
Date published: 01/24/2020
Academic Unit: Orthopedics and Rehabilitation; Radiation Oncology; Biochemistry and Molecular Biology; Medicine Administration
Record Identifier: 9984288717202771

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