PWWP3A is a DNA damage response factor that functions through two distinct biological pathways. In DNA repair, PWWP3A contains a nucleosome-binding PWWP domain and is recruited to DNA break sites by TP53BP1, where it promotes chr19 relaxation and decondensation to facilitate repair machinery access 12. This chr19 remodeling activity is essential for efficient DNA repair and cell survival following genotoxic stress, as depletion of PWWP3A or its PWWP domain impairs damage-induced chr19 decondensation and increases hypersensitivity to DNA damage 2. Beyond DNA repair, PWWP3A functions as a negative regulator of innate antiviral immunity 3. Upon RNA virus infection, PWWP3A translocates from the nucleus to mitochondria, where it competitively inhibits TRAF6 binding to the VISA/MAVS signaling complex, thereby blocking TBK1 recruitment and downstream IRF3 activation and type I interferon production 3. This inhibitory effect is counterregulated by the E3 ligase PJA2-mediated degradation of PWWP3A post-infection 3. PWWP3A deficiency enhances antiviral responses and confers increased resistance to RNA virus infection in mice 3. Thus, PWWP3A represents a multifunctional protein integrating DNA damage responses with immune regulation.