Unveiling a novel cellular stress response mechanism to photodamage

Ultraviolet (UV) radiation, a component of sunlight, holds both advantageous anddetrimental effects on human health. While shorter wavelengths of UV radiationaid in melanin and vitamin D synthesis, longer wavelengths pose risks like skincancer and premature aging due to DNA damage. To combat such stress, cellsemploy various mechanisms, including the heat shock response (HSR). Activation of this response involves a highly regulated transcriptional processorchestrated by heat shock factors (HSFs). While HSF1 has been observed as a keytranscription factor for HSR, other HSFs are also found to be associated withdiverse cellular functions, including stress responses. Here, we discuss arecent study by Feng et al., published in Clinical and Translational Medicine, shedding light on the novel function of HSF4 in regulating inflammation and senescence following UV exposure. The researchers observed acomplex of HSF4 and the cofactor COIL (Coilin) at R-loops–aberrant DNA-RNAhybrid structures arising from UV-induced DNA damage in human skin cells. Inthe study, they proposed the HSF4-COIL complex at R-loops as a potential therapeutic target to mitigate UV-induced skin damage.