p53-dependent chromatin relaxation is required for DNA double-strand break repair

Hongyu Chen, Jin Shan, Wenjing Qi, Lili Chen, and Xianlu Zeng

The tumor suppressor p53, a key transcription factor, plays a central role in cellular responses to DNA damage. In this study, we reveal a previously underappreciated role of p53 as an immediate responder to DNA double-strand breaks (DSBs), redefining it as an active participant in the earliest steps of DNA repair rather than solely a downstream transcriptional regulator. The cover illustration symbolically depicts this process: sunlight represents genotoxic stress (e.g., irradiation), and the electrical cables symbolize genomic DNA. Upon damage, DNA damage sensing machinery (workers) immediately arrive at the break site. An X-shaped cartoon figure represents p53, rapidly recruited to both proximal and distal chromatin flanking the break. By promoting chromatin relaxation, p53 facilitates the recruitment of repair proteins (depicted as purple and green semicircles) which then access and resolve the lesion.

This cover is designed by Yinxi Zhou and Jianfeng Jin from Hainan Medical University.