Identification of a new function for the cancer-associated gene PHF6 in the response of our cells to damaged DNA
In this week's issue of the international scientific journal EMBO Reports, a study led by Dr. Daniël Warmerdam (Cancer Center Amsterdam, The Netherlands) and Dr. Veronique Smits (Hospital Universitario de Canarias, Tenerife, Spain), reports the PHF6 protein as a novel factor involved in resuming cell growth after the repair of DNA that was damaged by ionizing radiation. Our genetic material, the DNA, is constantly threatened by processes of the cell itself and a variety of environmental factors, such as irradiation. If left unrepaired, damaged DNA can eventually lead to tumorigenesis, the process of transformation of normal cells into cancer cells.
To study how PHF6 contributes to the response after damaging the DNA, the researchers examined different processes involved in the detection of DNA damage, in the absence of PHF6. For this, they generated cells without the protein, through CRISPR technology. The study shows that cells without PHF6 have more damaged DNA because a critical pathway in the repair of DNA that is damaged by irradiation, called classical non-homologous end joining, is affected. These experiments demonstrate that PHF6 is required for protecting our genetic material by regulating this repair pathway.
The gene that encodes for PHF6 was frequently found to be mutated in several forms of leukemia, including T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). The results obtained in this study contribute to our knowledge of the cellular responses to factors that damage our DNA damage, which is critical for understanding how tumor formation takes place and might help in the development of new strategies for the detection and treatment of cancer. PHF6 is also mutated in patients with the Börjeson-Forssman-Lehmann syndrome, which is characterized by intellectual disability, obesity, and abnormal facial features. It remains unclear whether the function of PHF6 in DNA repair is also related to this syndrome.
This work was performed by researchers from the Cancer Center Amsterdam, Unidad de Investigación of the Hospital Universitario de Canarias, Netherlands Cancer Institute and Leiden University Medical Center, and was supported by funding from the Cancer Center Amsterdam; Ministerio de Ciencia, Innovación y Universidades; Agencia Canaria de Investigación, Innovación y Sociedad de la Información del Gobierno De Canarias; European Research Council and Netherlands Organisation for Scientific Research.
Publication: “PHF6 promotes non-homologous end joining and G2 checkpoint recovery”. Daniël O. Warmerdam, Ignacio Alonso-de Vega, Wouter W. Wiegant, Bram van den Broek, Magdalena B. Rother, Rob M.F. Wolthuis, Raimundo Freire, Haico van Attikum, René H. Medema and Veronique A.J. Smits. EMBO Reports, online 29 November 2019, DOI: 10.15252/embr.201948460.