Tumor protein p53-binding protein 1 (53BP1)

Tumor protein p53-binding protein 1 (53BP1) is a critical scaffold protein in the DNA damage response (DDR) that functions as a key regulator of DNA double-strand break (DSB) repair pathway choice. It primarily promotes non-homologous end joining (NHEJ) by protecting DNA ends from resection, thereby inhibiting the alternative homologous recombination (HR) pathway [2, 3]. 53BP1 is recruited to damaged chromatin through the recognition of specific histone marks, such as H4K20me2 and H2AK15ub, where it forms distinct nuclear foci that serve as biomarkers for DNA damage [12, 16]. In clinical oncology, 53BP1 is a major determinant of response to PARP inhibitors; its loss in BRCA1-deficient tumors is a well-documented mechanism of acquired drug resistance [3, 5]. Beyond cancer, 53BP1 is essential for physiological processes like V(D)J recombination and telomere protection [3, 4]. Current therapeutic strategies explore 53BP1 antagonists to overcome PARP inhibitor resistance or to enhance the precision of CRISPR-Cas9-mediated genome editing by shifting repair toward the high-fidelity HR pathway [2, 3].

Other names

TP53BP1p53-binding protein 1Tumor suppressor p53-binding protein 1TDRD30p202

Modulation of DNA double-strand break repair pathway choice by inhibiting 53BP1 to promote homologous recombination or sensitize cells to DNA-damaging agents.