High impact information on Trp53bp1

• Using a human cell line that faithfully recapitulated the Chk2-p53-PUMA pathway, we show that USP28 is required to stabilize Chk2 and 53BP1 in response to DNA damage [1].
• Recruitment of p53 binding protein 1 (53BP1) and Rad51 to sites of DNA lesion is impaired in Zmpste24-/- MEFs and in HGPS fibroblasts, resulting in delayed checkpoint response and defective DNA repair [2].
• The acceleration of NHEJ was unlikely to be due to increased presence of 53BP1 and Mre11 in TIFs, since knockdown of neither factor affected telomere fusions [3].
• The current findings, in combination with the known 53BP1 functions and how it is activated, implicate the DNA damage response to DSBs in the joining phase of class-switch recombination [4].
• We now examine potential functions for 53BP1 in the specific genomic alterations that occur in B lymphocytes [4].

Biological context of Trp53bp1

• p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice [5].
• 53BP1(-/-) cells show a slight S-phase checkpoint defect and prolonged G(2)/M arrest after treatment with ionizing radiation [5].
• 53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis [6].
• We propose that 53BP1, in the context of p53 deficiency, suppresses T cell lymphomagenesis through its roles in both cell-cycle checkpoints and double-stranded break repair [6].
• p53-binding protein 1 (53BP1) participates in the cellular response to DNA double-stranded breaks where it associates with various DNA repair/cell cycle factors including the H2AX histone variant [6].

Anatomical context of Trp53bp1

• GFP-M protein forms foci in mouse embryonic fibroblast cells lacking functional endogenous 53BP1 [7].
• RT-PCR analysis revealed that p53BP1 was expressed specifically in fully grown oocytes, as was HDAC4 [8].

Associations of Trp53bp1 with chemical compounds

• Aside from p53, we here identify 53BP1 as a critical mediator of nutlin-3-induced cytotoxicity [9].

Physical interactions of Trp53bp1

• 53BP1 is a p53 binding protein of unknown function that binds to the central DNA-binding domain of p53 [5].

Enzymatic interactions of Trp53bp1

• p53-binding protein-1 (53BP1) is phosphorylated in response to DNA damage and rapidly relocalizes to presumptive sites of DNA damage along with Mre11 and the phosphorylated histone 2A variant, gamma-H2AX [10].

Other interactions of Trp53bp1

• These data indicate that 53BP1 acts downstream of ATM and upstream of Chk2 in the DNA damage response pathway and is involved in tumor suppression [5].
• Moreover, activated B cells deficient for ATM, 53BP1, or MDC1, which interact with H2AX during the DSB response, show similarly increased IgH locus breaks and translocations [11].
• 53BP1 links DNA damage-response pathways to immunoglobulin heavy chain class-switch recombination [4].
• Although 53BP1 was dispensable for V(D)J recombination and somatic hypermutation (SHM), the processes by which immunoglobulin (Ig) variable region exons are assembled and mutated, it was required for Igh class-switch recombination (CSR), the recombination and deletion process by which Igh constant region genes are exchanged [4].
• One of the trapped genes was endoglin, an endothelial-specific transforming growth factor-beta type III receptor, and another was ASPP1, a p53-binding protein [12].

Analytical, diagnostic and therapeutic context of Trp53bp1

• By generating mice defective in m53BP1 (m53BP1(tr/tr)), we have created an animal model to further explore its biochemical and genetic roles in vivo [10].

References