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Updated: Jun 13, 2026
Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
Published on: January 31, 2018
Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response
Maayan Salton1, Yaniv Lerenthal, Shih-Ya Wang
1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract:
The DNA damage response (DDR) is a complex signaling network that is induced by DNA lesions and vigorously activated by double strand breaks (DSBs). The DSB response is mobilized by the nuclear protein kinase ATM, which phosphorylates key players in its various branches. SFPQ (PSF) and NONO (p54) are nuclear proteins that interact with each other and have diverse roles in nucleic acids metabolism. The SFPQ/NONO heterodimer was previously found to enhance DNA strand break rejoining in vitro. Our attention was drawn to these two proteins as they interact with the nuclear matrix protein Matrin 3 (MATR3), which we found to be a novel ATM target. We asked whether SFPQ and NONO too are involved in the DSB response. Proteins that function at the early phase of this response are often recruited to the damaged sites. We observed rapid recruitment of SFPQ/NONO to sites of DNA damage induced by laser microbeam. In MATR3 knockdown cells SFPQ/NONO retention at DNA damage sites was prolonged. SFPQ and MATR3 depletion led to abnormal accumulation of cells at the S-phase of the cell cycle following treatment with the radiomimetic chemical neocarzinostatin. Notably, proteins involved in DSB repair via nonhomologous end-joining co-immunoprecipitated with NONO; SFPQ depletion delayed DSB repair. Collectively the data suggest that SFPQ, NONO and MATR3 are involved in the early stage of the DSB response, setting the scene for DSB repair.
Insights
The study reveals that SFPQ, NONO, and MATR3 proteins are crucial for the early DNA damage response, particularly double-strand break (DSB) repair. Their recruitment to damaged DNA sites and involvement in cell cycle regulation highlight their role in maintaining genomic stability.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The DNA damage response (DDR) is a critical cellular process for maintaining genomic integrity, activated by DNA lesions like double-strand breaks (DSBs).
- ATM (ataxia-telangiectasia mutated) is a key kinase orchestrating the DDR, phosphorylating numerous downstream targets.
- SFPQ (Splicing Factor Pro-rich domain-containing protein) and NONO (Non-POU domain-containing octamer-binding protein) are nuclear proteins with known roles in nucleic acid metabolism and previously shown to enhance DNA repair in vitro.
Purpose of the Study:
- To investigate the involvement of SFPQ and NONO proteins in the cellular response to DNA double-strand breaks (DSBs).
- To determine if SFPQ, NONO, and their interacting partner MATR3 (Matrin 3) function in the early stages of DSB repair.
Main Methods:
- Utilized laser microbeam irradiation to induce localized DNA damage and observed protein recruitment using microscopy.
- Employed knockdown strategies for MATR3 and SFPQ to assess their impact on SFPQ/NONO localization and cell cycle progression.
- Performed co-immunoprecipitation assays to identify proteins interacting with NONO, particularly those involved in non-homologous end-joining (NHEJ).
Main Results:
- SFPQ and NONO were rapidly recruited to sites of laser-induced DNA damage.
- MATR3 knockdown led to prolonged retention of SFPQ/NONO at DNA damage sites.
- Depletion of SFPQ or MATR3 caused abnormal S-phase cell cycle accumulation after treatment with the radiomimetic agent neocarzinostatin.
- SFPQ depletion resulted in delayed DSB repair, and proteins involved in NHEJ were found to co-immunoprecipitate with NONO.
Conclusions:
- SFPQ, NONO, and MATR3 are integral components of the early DNA double-strand break (DSB) response.
- These proteins play a role in facilitating the initial steps of DSB repair, potentially by organizing the DNA damage site.
- The findings suggest a coordinated function of SFPQ, NONO, and MATR3 in orchestrating the cellular response to DNA damage and maintaining genome stability.
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