PALB2
Template:PBB Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.[1][2][3]
Function
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.[1] PALB2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulates strand invasion a vital step of homologous recombination.[4] PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.[4]
Clinical significance
Variants in the PALB2 gene are associated with an increased risk of developing breast cancer [5] and PALB2-deficient cells are sensitive to PARP inhibitors. [4]
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.[6] Tests for PALB2 have been developed by Ambry Genetics [7]and Myriad Genetics[8] that are now available.
Biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia.[3]
See also
References
- ^ a b "Entrez Gene: PALB2 partner and localizer of BRCA2".
- ^ Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM (June 2006). "Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2". Mol. Cell. 22 (6): 719–29. doi:10.1016/j.molcel.2006.05.022. PMID 16793542.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP (February 2007). "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2". Nat. Genet. 39 (2): 159–61. doi:10.1038/ng1942. PMID 17200672.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b c Buisson R, Dion-Côté AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY (2010). "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination". Nature Structural & molecular biology. 17 (10): 1247–54. doi:10.1038/nsmb.1915. PMID 20871615.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Chen P, Liang J, Wang Z, Zhou X, Chen L, Li M, Xie D, Hu Z, Shen H, Wang H (September 2008). "Association of common PALB2 polymorphisms with breast cancer risk: a case-control study". Clin. Cancer Res. 14 (18): 5931–7. doi:10.1158/1078-0432.CCR-08-0429. PMID 18794107.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP (2009). "Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene". Science. 324 (5924): 217. doi:10.1126/science.1171202. PMC 2684332. PMID 19264984.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Ambry Genetics".
- ^ "Myriad Genetics".
Further reading
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM (2006). "Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2". Mol. Cell. 22 (6): 719–29. doi:10.1016/j.molcel.2006.05.022. PMID 16793542.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR (2007). "PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene". Nat. Genet. 39 (2): 165–7. doi:10.1038/ng1959. PMC 2871593. PMID 17200668.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N (2007). "Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer". Nat. Genet. 39 (2): 162–4. doi:10.1038/ng1947. PMID 17200671.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP (2007). "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2". Nat. Genet. 39 (2): 159–61. doi:10.1038/ng1942. PMID 17200672.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R (2007). "A recurrent mutation in PALB2 in Finnish cancer families". Nature. 446 (7133): 316–9. doi:10.1038/nature05609. PMID 17287723.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Tischkowitz M, Xia B, Sabbaghian N, Reis-Filho JS, Hamel N, Li G, van Beers EH, Li L, Khalil T, Quenneville LA, Omeroglu A, Poll A, Lepage P, Wong N, Nederlof PM, Ashworth A, Tonin PN, Narod SA, Livingston DM, Foulkes WD (2007). "Analysis of PALB2/FANCN-associated breast cancer families". Proc. Natl. Acad. Sci. U.S.A. 104 (16): 6788–93. doi:10.1073/pnas.0701724104. PMC 1871863. PMID 17420451.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Oliver AW, Swift S, Lord CJ, Ashworth A, Pearl LH (2009). "Structural basis for recruitment of BRCA2 by PALB2". EMBO Reports. 10 (9): 990–6. doi:10.1038/embor.2009.126. PMC 2750052. PMID 19609323.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
 | This article on a gene on human chromosome 16 is a stub. You can help Wikipedia by expanding it. |