Reference Detail

Ref Type

Journal Article

PMID

(20871615)

Authors

Buisson R, Dion-Cote AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY

Title

Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Nature structural & molecular biology	17	10	2010 Oct	1247-54	Nat Struct Mol Biol

URL

Abstract Text

Inherited mutations in human PALB2 are associated with a predisposition to breast and pancreatic cancers. PALB2's tumor-suppressing effect is thought to be based on its ability to facilitate BRCA2's function in homologous recombination. However, the biochemical properties of PALB2 are unknown. Here we show that human PALB2 binds DNA, preferentially D-loop structures, and directly interacts with the RAD51 recombinase to stimulate strand invasion, a vital step of homologous recombination. This stimulation occurs through reinforcing biochemical mechanisms, as PALB2 alleviates inhibition by RPA and stabilizes the RAD51 filament. Moreover, PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion. Finally, we show that PALB2-deficient cells are sensitive to PARP inhibitors. Our studies provide the first biochemical insights into PALB2's function with piBRCA2 as a mediator of homologous recombination in DNA double-strand break repair.

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Molecular Profile	Treatment Approach
PALB2 R1086*	PARP Inhibitor (Pan)
PALB2 T351Rfs*4	PARP Inhibitor (Pan)
PALB2 Q988*	PARP Inhibitor (Pan)
PALB2 Y28C	PARP Inhibitor (Pan)
PALB2 K25*	PARP Inhibitor (Pan)
PALB2 S859*	PARP Inhibitor (Pan)
PALB2 P113Qfs*64	PARP Inhibitor (Pan)
PALB2 S64L	PARP Inhibitor (Pan)
PALB2 W1140G	PARP Inhibitor (Pan)
PALB2 E230*	PARP Inhibitor (Pan)
PALB2 L35F	PARP Inhibitor (Pan)
PALB2 del	PARP Inhibitor (Pan)
PALB2 V410A	PARP Inhibitor (Pan)
PALB2 R414K	PARP Inhibitor (Pan)
PALB2 E3*	PARP Inhibitor (Pan)
PALB2 L24S	PARP Inhibitor (Pan)
PALB2 L947S	PARP Inhibitor (Pan)
PALB2 M723Vfs*21	PARP Inhibitor (Pan)
PALB2 R131fs	PARP Inhibitor (Pan)
PALB2 N821Tfs*25	PARP Inhibitor (Pan)
PALB2 W912G	PARP Inhibitor (Pan)
PALB2 L1027R	PARP Inhibitor (Pan)
PALB2 C77Vfs*100	PARP Inhibitor (Pan)
PALB2 R414Q	PARP Inhibitor (Pan)
PALB2 P1009Lfs*6	PARP Inhibitor (Pan)
PALB2 R753*	PARP Inhibitor (Pan)
PALB2 E181*	PARP Inhibitor (Pan)
PALB2 K346Tfs*13	PARP Inhibitor (Pan)
PALB2 Q251*	PARP Inhibitor (Pan)
PALB2 N497Mfs*64	PARP Inhibitor (Pan)
PALB2 T413Hfs*11	PARP Inhibitor (Pan)
PALB2 R414A	PARP Inhibitor (Pan)
PALB2 Q60Rfs*7	PARP Inhibitor (Pan)
PALB2 Q790*	PARP Inhibitor (Pan)
PALB2 G1043D	PARP Inhibitor (Pan)
PALB2 K862Rfs*9	PARP Inhibitor (Pan)
PALB2 F440fs	PARP Inhibitor (Pan)
PALB2 L659Qfs*3	PARP Inhibitor (Pan)
PALB2 T494Lfs*67	PARP Inhibitor (Pan)
PALB2 Q348*	PARP Inhibitor (Pan)
PALB2 Y1183*	PARP Inhibitor (Pan)
PALB2 S417A	PARP Inhibitor (Pan)
PALB2 G808*	PARP Inhibitor (Pan)
PALB2 W1038*	PARP Inhibitor (Pan)
PALB2 R414*	PARP Inhibitor (Pan)
PALB2 I1037T	PARP Inhibitor (Pan)
PALB2 R170Ifs*14	PARP Inhibitor (Pan)
PALB2 L961P	PARP Inhibitor (Pan)
PALB2 P1097R	PARP Inhibitor (Pan)
PALB2 K908fs	PARP Inhibitor (Pan)
PALB2 S254Ifs*3	PARP Inhibitor (Pan)
PALB2 G1043V	PARP Inhibitor (Pan)
PALB2 Y28P	PARP Inhibitor (Pan)
PALB2 R421A	PARP Inhibitor (Pan)
PALB2 S779*	PARP Inhibitor (Pan)
PALB2 K1048Rfs*27	PARP Inhibitor (Pan)
PALB2 L21P	PARP Inhibitor (Pan)
PALB2 E837*	PARP Inhibitor (Pan)
PALB2 R37H	PARP Inhibitor (Pan)
PALB2 L24P	PARP Inhibitor (Pan)
PALB2 E1010*	PARP Inhibitor (Pan)
PALB2 K142Nfs*35	PARP Inhibitor (Pan)
PALB2 Y409*	PARP Inhibitor (Pan)
PALB2 W898*	PARP Inhibitor (Pan)
PALB2 L35P	PARP Inhibitor (Pan)
PALB2 L1070P	PARP Inhibitor (Pan)
PALB2 E407*	PARP Inhibitor (Pan)
PALB2 Q1056*	PARP Inhibitor (Pan)
PALB2 inact mut	PARP Inhibitor (Pan)
PALB2 Q921Tfs*7	PARP Inhibitor (Pan)
PALB2 Y1108fs	PARP Inhibitor (Pan)
PALB2 Q151*	PARP Inhibitor (Pan)
PALB2 G937R	PARP Inhibitor (Pan)
PALB2 N344Tfs*2	PARP Inhibitor (Pan)
PALB2 M296*	PARP Inhibitor (Pan)
PALB2 P378Lfs*46	PARP Inhibitor (Pan)
PALB2 C882fs	PARP Inhibitor (Pan)
PALB2 K353Ifs*7	PARP Inhibitor (Pan)
PALB2 Q775*	PARP Inhibitor (Pan)
PALB2 H46Y	PARP Inhibitor (Pan)
PALB2 L947F	PARP Inhibitor (Pan)
PALB2 L671*	PARP Inhibitor (Pan)
PALB2 Y551*	PARP Inhibitor (Pan)
PALB2 E669fs	PARP Inhibitor (Pan)
PALB2 S387Lfs*14	PARP Inhibitor (Pan)
PALB2 loss	PARP Inhibitor (Pan)
PALB2 K1098*	PARP Inhibitor (Pan)
PALB2 A1025R	PARP Inhibitor (Pan)
PALB2 L1172P	PARP Inhibitor (Pan)
PALB2 F1181Lfs*54	PARP Inhibitor (Pan)
PALB2 P104L	PARP Inhibitor (Pan)
PALB2 G1043A	PARP Inhibitor (Pan)
PALB2 L24F	PARP Inhibitor (Pan)
PALB2 I944N	PARP Inhibitor (Pan)
PALB2 T413S	PARP Inhibitor (Pan)
PALB2 T413A	PARP Inhibitor (Pan)
PALB2 D595Mfs*4	PARP Inhibitor (Pan)
PALB2 S172fs	PARP Inhibitor (Pan)
PALB2 N280Tfs*8	PARP Inhibitor (Pan)
PALB2 Q1023*	PARP Inhibitor (Pan)
PALB2 L531Cfs*30	PARP Inhibitor (Pan)
PALB2 T1030I	PARP Inhibitor (Pan)
PALB2 K353Nfs*3	PARP Inhibitor (Pan)
PALB2 L972Q	PARP Inhibitor (Pan)
PALB2 S979Vfs*11	PARP Inhibitor (Pan)
PALB2 R1086Efs*9	PARP Inhibitor (Pan)
PALB2 K515*	PARP Inhibitor (Pan)
PALB2 L17P	PARP Inhibitor (Pan)

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PALB2 inact mut	Advanced Solid Tumor	sensitive	Olaparib	Preclinical	Actionable	In a preclinical study, Lynparza (olaparib) resulted in decreased cell survival in a PALB2 deficient cell line derived from a Fanconi anemia patient (PMID: 20871615).	20871615