Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''TP53BP1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Clinical significance

53BP1 is underexpressed in most cases of

triple-negative breast cancer Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e ...

DNA repair

DNA double-strand breaks (DSBs) are cytotoxic damages that can be repaired either by the

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...

al 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 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...

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 The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes Messenger RNA, mRNA and proteins in preparation for subsequ ...

of the

cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

, when a

sister chromatid A sister chromatid refers to the identical copies ( chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the du ...

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 Microhomology-mediated end joining (MMEJ), also known as alternative nonhomologous end-joining (Alt-NHEJ) is one of the pathways for repairing double-strand breaks in DNA. As reviewed by McVey and Lee, the foremost distinguishing property of MMEJ ...

, is highly inaccurate and likely contributes to the aging process.

Interactions

53BP1 has been shown to physically interact with: *

Histone H4 Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryote, eukaryotic cells. Featuring a main globular domain and a long N-terminus, N-terminal tail, H4 is involved with the structure of the nucleo ...

dimethylated or monomethylated at Lysine 20 *

Histone H2A Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. The other histone proteins are: Histone H1, H1, Histone H2B, H2B, Histone H3, H3 and Histone H4, H4. Background Histones are pro ...

or Histone H2A.X ubiquitinated at Lysine 15 *

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

* DYNLL1 * TIRR (NUDT16L1)

References

External links