TP53BP1

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Protein-coding gene in the species Homo sapiens

title: "TP53BP1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/TP53BP1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.

Clinical significance

53BP1 is underexpressed in most cases of triple-negative breast cancer.

DNA repair

DNA double-strand breaks (DSBs) are cytotoxic damages that can be repaired either by the homologous recombinational repair (HR) pathway or by the non-homologous end-joining (NHEJ) pathway. NHEJ, although faster than HR, is less accurate. The early divergent step between the two pathways is end resection, and this step is regulated by numerous factors. In particular, BRCA1 and 53BP1 play a role in determining the balance between the two pathways. 53BP1 restricts resection and promotes NHEJ.

Age-associated deficient repair

Ordinarily during the G1 phase of the cell cycle, when a sister chromatid is unavailable for HR, NHEJ is the predominant pathway for repairing DNA double-strand breaks (DSBs). However, as individuals age, recruitment of 53BP1 to DSBs during G1 becomes deficient. The absence of 53BP1 at such DSBs appears to promote the alternative error-prone repair process Alt-EJ. This repair process, also referred to as microhomology-mediated end joining, is highly inaccurate and likely contributes to the aging process.

Interactions

53BP1 has been shown to physically interact with:

  • Histone H4 dimethylated or monomethylated at Lysine 20{{cite journal | vauthors = Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G | title = Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair | journal = Cell | volume = 127 | issue = 7 | pages = 1361–73 | date = Dec 2006 | pmid = 17190600 | doi = 10.1016/j.cell.2006.10.043 | doi-access = free | pmc = 1804291 }}

  • Histone H2A or Histone H2A.X ubiquitinated at Lysine 15

  • p53

  • DYNLL1

  • TIRR (NUDT16L1){{cite journal | vauthors = Drané P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Münch C, Harper JW, Chaudhuri J, Soutoglou E, Mer G, Chowdhury D | title = TIRR regulates 53BP1 by masking its histone methyl-lysine binding function | journal = Nature | volume = 543 | issue = 7644 | pages = 211–6 | date = Mar 2017 | pmid = 28241136 | doi = 10.1038/nature21358 | doi-access = free | pmc = 5441565 | bibcode = 2017Natur.543..211D }}

References

References

  1. (Jun 1994). "Two cellular proteins that bind to wild-type but not mutant p53". Proceedings of the National Academy of Sciences of the United States of America.
  2. (Oct 1998). "Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2". The Journal of Biological Chemistry.
  3. "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1".
  4. (Jun 2010). "53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers". Nature Structural & Molecular Biology.
  5. (2014). "Double-strand break repair: 53BP1 comes into focus". Nat. Rev. Mol. Cell Biol..
  6. (2016). "DNA double-strand break repair: a tale of pathway choices". Acta Biochim. Biophys. Sin. (Shanghai).
  7. (December 2020). "Age-associated deficient recruitment of 53BP1 in G1 cells directs DNA double-strand break repair to BRCA1/CtIP-mediated DNA-end resection". Aging.
  8. (Jun 2013). "53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark". Nature.
  9. (Jul 2002). "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor". The EMBO Journal.
  10. (Mar 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis". Protein Science.
  11. (Mar 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development.
  12. (Oct 2002). "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor". Acta Crystallographica Section D.
  13. (Mar 2005). "The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation". The Journal of Biological Chemistry.
  14. (Jul 2018). "Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein". Nat Struct Mol Biol.

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