Partner and localizer of BRCA2, also known as PALB2 or FANCN, 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 ...

which in humans is encoded by the ''PALB2''

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 ...

Function

Homologous recombinational repair of DNA double-strand damage

This gene encodes a protein that functions in genome maintenance ( double strand break repair). This protein binds to and colocalizes with the breast cancer 2 early onset protein (

BRCA2 ''BRCA2'' and BRCA2 () are human genes and their protein products, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associate ...

) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2. PALB2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion, a vital step of

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 ...

, PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.

Clinical significance

Variants in the ''PALB2'' gene are associated with an increased risk of developing breast cancer of magnitude similar to that associated with BRCA2 mutations and ''PALB2''-deficient cells are sensitive to

PARP inhibitors PARP inhibitors are a class of drugs that are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP), which plays a role in repairing DNA in damaged cells. Medical uses of these drugs include the treatment of heri ...

. ''PALB2'' was recently identified as a susceptibility gene for familial

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

by scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins. This has paved for the way for developing a new gene test for families where pancreatic cancer occurs in multiple family members. Tests for PALB2 have been developed by Ambry Genetics and Myriad Genetics that are now available. Prophylactic

mastectomy Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer choose to have ...

should be considered for women that had breast cancer and a PALB2 mutation. Biallelic mutations in ''PALB2'' (also known as ''FANCN''), similar to biallelic ''BRCA2'' mutations, cause

Fanconi anemia Fanconi anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...

. Mutations in this gene have been associated with an increased risk of ovarian, breast and pancreatic cancer.

Meiosis

PALB2 mutant male mice have reduced fertility. This reduced fertility appears to be due to germ cell attrition resulting from a combination of unrepaired DNA breaks during

meiosis Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...

and defective

synapsis Synapsis or Syzygy is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of me ...

of the X and Y chromosomes. The function of

during meiosis appears to be repair of DNA damages, particularly double-strand breaks (also see Origin and function of meiosis). The PALB2-BRCA1 interaction is likely important for repairing such damages during male meiosis.

References

External links

*
PALB2 Interest Group
{{Webarchive, url=https://web.archive.org/web/20160112204526/http://www.palb2.org/ , date=2016-01-12 – research consortium Human proteins

Function

Clinical significance

Meiosis

See also

References

Further reading

External links