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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

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 a human gene and its protein product, 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 associated) ...

) 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 cellular organisms but may ...

, 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 group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on ...

. ''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 t ...

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 have the operat ...

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 anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of nor ...

. 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 (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...

and defective

synapsis Synapsis 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 meiosis. Whe ...

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 origin and function of meiosis are currently not well understood scientifically, and would provide fundamental insight into the evolution of sexual reproduction in eukaryotes. There is no current consensus among biologists on the questions of h ...

). The PALB2-BRCA1 interaction is likely important for repairing such damages during male meiosis.

References

External links

* {{PDBe-KB2, Q86YC2, Partner and localizer of BRCA2
PALB2 Interest Group
– research consortium

Function

Clinical significance

Meiosis

See also

References

Further reading

External links