Trp53bp1, also known as p53 binding protein 1, is a tumor suppressor that plays a crucial role in DNA repair pathways, especially at DNA double-strand breaks (DSBs). It nucleates the anti-end resection machinery, countering BRCA1 activity, and thus influencing the choice between homologous recombination (HR) and non-homologous end joining (NHEJ) [1,2,3,5]. It is also involved in processes like lymphocyte DNA end joining, which diversifies immune antigen receptors [3].

In BRCA1-deficient cells, loss of 53BP1 leads to DNA end processing and HR restoration, often causing resistance to PARP inhibitors [1]. In somatic cell reprogramming, inactivation of 53bp1 rescues reprogramming efficiency in Brca1-deficient cells as somatic cell reprogramming depends on BRCA1/2-mediated HDR of replication-associated DSBs [2]. Also, 53BP1 deficiency in mice and cells induces BIR-like hyperrecombination, associated with template switching and large deletions, highlighting its role in suppressing genome instability [4].

In conclusion, Trp53bp1 is essential for regulating DNA repair pathway choice at DSBs, with its loss having significant impacts on processes like tumor cell response to PARP inhibitors, somatic cell reprogramming, and genome stability. Studies using Trp53bp1 knockout models have provided valuable insights into its functions, especially in the context of cancer-related DNA repair dysregulation.