Trp53bp1, also known as p53 binding protein 1, is a tumor suppressor that plays a crucial role in DNA repair pathways, especially in regulating DNA end joining at double-strand breaks (DSBs) [3]. It nucleates the anti-end resection machinery, countering BRCA1 activity, and thus is involved in determining the choice between homology-directed repair (HDR) and non-homologous end joining (NHEJ) [1,2,3]. This function is vital for maintaining genome integrity and is relevant in processes such as lymphocyte immune antigen receptor diversification and somatic cell reprogramming [2,3].

In BRCA1-deficient cells, loss of 53BP1 leads to DNA end processing and HDR restoration, which is associated with increased micronuclei, cytoplasmic double-stranded DNA, activation of the cGAS-STING pathway, and enhanced anti-tumor immunity in ovarian and pancreatic cancer [1]. In somatic cell reprogramming, inactivation of 53BP1 restores HDR function and improves reprogramming efficiency in Brca1-deficient cells [2]. Also, 53BP1 deficiency causes hyperrecombination through break-induced replication (BIR), which is mutagenic and can lead to template switching and large deletions, highlighting its role in suppressing genome instability [4].

In conclusion, Trp53bp1 is essential for regulating DNA repair pathway choice, maintaining genome stability, and influencing processes like tumor immunogenicity and somatic cell reprogramming. Studies using 53BP1 loss-of-function models, especially in cancer-related research, have revealed its significance in cancer development, treatment resistance, and response to immunotherapy, providing potential directions for therapeutic strategies targeting these diseases.