PALB2

[5][6][7] This gene encodes a protein that functions in genome maintenance (double strand break repair).

[15] 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.

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

[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.

[citation needed] The PALB2-BRCA1 interaction is likely important for repairing such damages during male meiosis.

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.