PALB2

Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.^[5][6][7]

PALB2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2W18, 3EU7
Identifiers
Aliases	PALB2, FANCN, PNCA3, partner and localizer of BRCA2
External IDs	OMIM: 610355; MGI: 3040695; HomoloGene: 11652; GeneCards: PALB2; OMA:PALB2 - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p12.2 Start 23,603,160 bp[1] End 23,641,310 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F2 Start 121,706,485 bp[2] End 121,732,208 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte buccal mucosa cell gonad testicle Achilles tendon ventricular zone gingival epithelium ganglionic eminence amniotic fluid mucosa of transverse colon Top expressed in zygote secondary oocyte primary oocyte tail of embryo hand epiblast spermatocyte embryo genital tubercle yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein binding Cellular component nucleoplasm nucleus Biological process animal organ morphogenesis somitogenesis post-anal tail morphogenesis cellular response to DNA damage stimulus DNA recombination mesoderm development negative regulation of apoptotic process in utero embryonic development multicellular organism growth embryonic organ development inner cell mass cell proliferation DNA repair double-strand break repair via homologous recombination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79728 233826 Ensembl ENSG00000083093 ENSMUSG00000044702 UniProt Q86YC2 Q3U0P1 RefSeq (mRNA) NM_024675 NM_001081238 NM_001289842 NM_001289843 NM_001289844 NM_001289845 NM_172744 RefSeq (protein) NP_078951 NP_001074707 NP_001276771 NP_001276772 NP_001276773 NP_001276774 Location (UCSC) Chr 16: 23.6 – 23.64 Mb Chr 7: 121.71 – 121.73 Mb PubMed search [3] [4]
Wikidata
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Function

Characterized domaines of PALB2

Recombinational repair of DNA double-strand damage - some key steps. ATM (ATM) is a protein kinase that is recruited and activated by DNA double-strand breaks. DNA double-strand damages also activate the Fanconi anemia core complex (FANCA/B/C/E/F/G/L/M).^[8] The FA core complex monoubiquitinates the downstream targets FANCD2 and FANCI.^[9] ATM activates (phosphorylates) CHEK2 and FANCD2^[10] CHEK2 phosphorylates BRCA1.^[11] Ubiquinated FANCD2 complexes with BRCA1 and RAD51.^[12] The PALB2 protein acts as a hub,^[13] bringing together BRCA1, BRCA2 and RAD51 at the site of a DNA double-strand break, and also binds to RAD51C, a member of the RAD51 paralog complex RAD51B-RAD51C-RAD51D-XRCC2 (BCDX2). The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.^[14] RAD51 plays a major role in homologous recombinational repair of DNA during double strand break repair. In this process, an ATP dependent DNA strand exchange takes place in which a single strand invades base-paired strands of homologous DNA molecules. RAD51 is involved in the search for homology and strand pairing stages of the process.

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) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2.^[5] PALB2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion, a vital step of homologous recombination,^[15] PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.^[15]

Clinical significance

Variants in the PALB2 gene are associated with an increased risk of developing breast cancer ^[16] of magnitude similar to that associated with BRCA2 mutations ^[17] and PALB2-deficient cells are sensitive to PARP inhibitors.^[15]

PALB2 was recently identified as a susceptibility gene for familial pancreatic cancer 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.^[18] Tests for PALB2 have been developed by Ambry Genetics ^[19] and Myriad Genetics^[20] that are now available.

Prophylactic mastectomy should be considered for women that had breast cancer and a PALB2 mutation.^[21][22]

Biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia.^[7]

Mutations in this gene have been associated with an increased risk of ovarian, breast and pancreatic cancer.^[23]

Meiosis

PALB2 mutant male mice have reduced fertility.^[24] This reduced fertility appears to be due to germ cell attrition resulting from a combination of unrepaired DNA breaks during meiosis and defective synapsis of the X and Y chromosomes. The function of homologous recombination during meiosis appears to be repair of DNA damages, particularly double-strand breaks (also see Origin and function of meiosis).^{[citation needed]} The PALB2-BRCA1 interaction is likely important for repairing such damages during male meiosis.

See also

• Fanconi anemia
• BRCA2
• DNA repair
• Tumor suppressor gene