Partner and localizer of BRCA2

Definition:

Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. Strongly stimulates the DNA strand-invasion activity of RAD51, stabilizes the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51. Serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is essential for homologous recombination. Via its WD repeats is proposed to scaffold a HR complex containing RAD51C and BRCA2 which is thought to play a role in HR-mediated DNA repair. Essential partner of BRCA2 that promotes the localization and stability of BRCA2. Also enables its recombinational repair and checkpoint functions of BRCA2. May act by promoting stable association of BRCA2 with nuclear structures, allowing BRCA2 to escape the effects of proteasome-mediated degradation. Binds DNA with high affinity for D loop, which comprises single-stranded, double-stranded and branched DNA structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with BRCA2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity.

References:

[1]. Rémi Buisson, et al. PALB2 self-interaction controls homologous recombination. Nucleic Acids Res. 2012 Nov 1;40(20):10312-23. [Content Brief]

[2]. T K Foo, et al. Compromised BRCA1-PALB2 interaction is associated with breast cancer risk. Oncogene. 2017 Jul 20;36(29):4161-4170. [Content Brief]

[3]. Bing Xia, et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2006 Jun 23;22(6):719-729. [Content Brief]

[4]. Eloïse Dray, et al. Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2. Nat Struct Mol Biol. 2010 Oct;17(10):1255-9. [Content Brief]

[5]. Shirley M-H Sy, et al. PALB2 regulates recombinational repair through chromatin association and oligomerization. J Biol Chem. 2009 Jul 3;284(27):18302-10. [Content Brief]

[6]. Rémi Buisson, et al. Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination. Nat Struct Mol Biol. 2010 Oct;17(10):1247-54. [Content Brief]

[7]. Shirley M H Sy, et al. PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7155-60. [Content Brief]

[8]. J-Y Park, et al. Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair. Oncogene. 2014 Oct 2;33(40):4803-12. [Content Brief]

[9]. Rémi Buisson, et al. Breast cancer proteins PALB2 and BRCA2 stimulate polymerase η in recombination-associated DNA synthesis at blocked replication forks. Cell Rep. 2014 Feb 13;6(3):553-64. [Content Brief]

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