53BP1, DNA Damage Response and Tumor Suppression

Mon, 09/23/2013 - 10:46

53BP1 (p53 binding protein 1) was originally thought to be a p53 transcriptional enhancing partner, but now has been shown to be an ataxia telangiectasia mutated (ATM) substrate. It is a late DNA damage response (DDR) marker, appearing in the telophase/cytokinesis phase in mitotic mammalian cells (1). 53BP1 antibody was employed to show the absence of a full DDR response in mitotic cells – this response is also suppressed by high levels of cyclin-dependent kinase1 (CDK1) activation. Another cell cycle study involving 53BP1 antibody focused on characterizing those genomic loci within metaphase chromosomes that are prone to gaps and breaks, also known as common fragile sites (2).  Their findings suggest a model of DNA damage where the formation of large nuclear bodies containing 53BP1, MCD1, and OPT domains is triggered in G1 cells in response to replication inhibitors such as aphidicolin. Recruitment of 53BP1 to DNA damage sites within cells is known to involve the ubiquitination cascade, but research using 53BP1 antibody was able to pinpoint the degradation of the JMJD2A tandem tudor domain by the E3 ubiquitin ligase RNF8 as a controlling mechanism (3). Additional 53BP1 antibody DNA damage experiments were performed in rat embryos generated from damaged paternal genomes exposed to cyclophosphamide, an anticancer alkylating agent (4).

Immunocytochemistry/Immunofluorescence: 53BP1 Antibody Immunocytochemistry/Immunofluorescence: 53BP1 Antibody

In immunofluorescent studies with 53BP1 antibody, Reichert et al found that the IAP Survivin must not only accumulate in the nucleus, but also interact with the double-strand break (DSB) machinery to regulate DSB damage repair in glioblastoma cells following irradiation (5).

  1. PMID: 21878640
  2. PMID: 21444690
  3. PMID: 22373579
  4. PMID: 22454429
  5. PMID: 21852011

Novus Biologicals offers various 53BP1 reagents for your research needs including:

Blog Topics