TP53BP1

Description

The TP53BP1 (tumor protein p53 binding protein 1) is a protein-coding gene located on chromosome 15.

TP53BP1, also known as p53-binding protein 1 or 53BP1, is a protein involved in the repair of double-strand breaks (DSBs) in DNA. It plays a key role in determining the balance between the homologous recombinational repair (HR) pathway and the non-homologous end-joining (NHEJ) pathway. TP53BP1 restricts resection and promotes NHEJ, which is particularly important during the G1 phase of the cell cycle when a sister chromatid is unavailable for HR. However, the recruitment of TP53BP1 to DSBs during G1 becomes deficient with age, promoting an alternative, error-prone repair process known as Alt-EJ. This process contributes to the aging process. TP53BP1 is underexpressed in most cases of triple-negative breast cancer.

TP53BP1, also known as 53BP1, is a protein involved in the repair of double-strand breaks (DSBs) in DNA, specifically by promoting the non-homologous end joining (NHEJ) pathway. It counteracts the function of the homologous recombination (HR) repair protein BRCA1, ensuring that NHEJ is prioritized. When DNA damage occurs, ATM phosphorylation triggers interactions with RIF1 and the release from NUDT16L1/TIRR, allowing TP53BP1 to move to DSB sites. TP53BP1 recognizes and binds to specific histone modifications at DSB sites, including monoubiquitinated H2A at Lys-15 (H2AK15Ub) and dimethylated H4 at Lys-20 (H4K20me2). Beyond DNA repair, TP53BP1 plays a vital role in immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that requires DNA DSBs. While not directly involved in classic NHEJ or V(D)J recombination, TP53BP1 contributes to the repair and orientation of broken DNA ends during CSR. Additionally, it promotes NHEJ of dysfunctional telomeres through interaction with PAXIP1. This protein forms homoligomers and interacts with various other proteins, including p53, DCLRE1C, and various histone modifications.

TP53BP1 is also known as 53BP1, TDRD30, p202, p53BP1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing