NONO: Key Protein in UV Radiation Response and Cancer Prevention

NONO: Key Protein in UV Radiation Response and Cancer Prevention

A new study published in the journal Oncogene revealed that a protein called NONO plays a crucial role in the cellular response against the detrimental effects of UV radiation in DNA strands. The study entitled “NONO regulates the intra-S-phase checkpoint in response to UV radiation” was conducted by researchers at Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia, and the Italian Istituto Nazionale Tumori “Fondazione G. Pascale”- IRCCS, University of Siena and Istituto Toscano Tumori (ITT).

Melanoma is the most dangerous form of skin cancer, usually caused by damage to skin cells (usually by ultraviolet radiation from sunshine or tanning beds), which triggers mutations that are not repaired allowing cells to rapidly multiply and generate malignant tumors.

Exposure to ultraviolet radiation, the main risk factor for skin cancer, can cause DNA damage. Cells respond to UV-induced DNA damage by activating different internal checkpoints which arrest the cell cycle and activate DNA repair mechanisms to prevent the damaged DNA from being replicated and passed onto daughter cells.

NONO, a multifunctional cellular protein, was recently found to be involved in DNA repair mechanisms. Interestingly, this protein was found to be mutated in several types of cancer and has been suggested as an important factor influencing melanoma development and progression. In the study, researchers assessed the role played by NONO in the cellular response to UV radiation and its possible link to lesions and malignant tumors.

The team found that silencing NONO protein expression in normal cells decreases cellular growth rate and impairs cell’s checkpoint response. In cells exposed to UV radiation and in a melanoma cell lines, the absence of NONO resulted in the absence of cell cycle checkpoints’ activation and subsequent DNA replication – including damaged DNA – without the activation of DNA repair pathways.

The research team concluded that NONO plays a crucial role in mediating the cellular response to UV-induced DNA damage, ultimately preventing cancer development. “Our study provides an important missing link which contributes to further dissecting the complex cascade of events that orchestrate the cellular response to DNA damage,” noted the study’s lead author Dr. Luigi Alfano in a news release.

“Considering that many studies are identifying NONO alterations in cancer, our findings will likely help to shed light on the molecular mechanisms of tumorigenesis, especially in tumor types like melanoma, in which exposure to UV radiation plays such a prominent part. Our work also provides the preclinical framework supporting the development of new agents targeting NONO that could be used to sensitize cancer cells to a variety of drugs that cause DNA damage, such as common chemotherapy agents,” concluded the study’s co-senior author Dr. Francesca Pentimalli.

Leave a Comment