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FLASH GENE
Symbol PALB2 contributors: mct/npt/pgu - updated : 02-02-2015
HGNC name partner and localizer of BRCA2
HGNC id 26144
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal coiled-coil motif of PALB2 regulates its self-association and homologous recombination
  • shares with NFE2L2 a highly conserved ETGE-type KEAP1 binding motif
  • mono polymer homomer , oligo
    HOMOLOGY
    Homologene
    FAMILY
  • BRCA2/RAD51 complex
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • required with BRCA2 for homologous recombination repair and necessary for the correct association of BRCA2 with chromatin
  • integral component of the BRCA complex important for recombinational DNA repair
  • molecular scaffold in the formation of BRCA1-PALB2-BRCA2 complex
  • not only regulates the efficiency of homologous recombination but also dictates the specific homologous recombination pathway in which it participates
  • central core of a BRCA1
  • PALB2
    BRCA2 complex essential for homologous recombination
  • can work in concert with a BRCA2 construct to further promote D-loop formation
  • important regulator of homologous recombination
  • crucial mediator of homologous recombination in cells, thus providing a plausible mechanism for the development of cancer
  • multifaceted role of PALB2 in chromosome damage repair
  • stabilizes BRCA2 by promoting its chromatin association
  • stimulates the ability of RAD51 to make D loops
  • BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage
  • regulator of cellular redox homeostasis and provide a new link between oxidative stress and the development of cancer and Fanconi anemia
  • essential for BRCA2 anchorage to nuclear structures and for homologous recombinational repair of DNA double-strand breaks
  • required for DNA repair by homologous recombination (HR)
  • may link HR to a key ubiquitin-related signaling pathway that responds to DSBs
  • CELLULAR PROCESS nucleotide, repair, recombination
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • member of the group III Fanconi anemia proteins, with BRCA1 and FANCJ (BRIP1), which do not play a role in FANCD2 monoubiquitination
  • homo-oligomerization is essential for its focal accumulation at DNA breaks to secure the BRCA2-RAD51 repair machinery
  • INTERACTION
    DNA binds DNA, preferentially D-loop structures
    RNA
    small molecule
    protein
  • interaction partner of BRCA2 (BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity)
  • binding directly to BRCA1
  • interacting with MORF4L1 (abrogation of the PALB2-MORF4L1 interaction resulted in elevated sister chromatid exchange frequencies)
  • PALB2 binds directly to a conserved chromodomain protein, MORF4L1, which is a component of histone acetyltransferase-deacetylase complexes
  • directly interacts with the RAD51 recombinase to stimulate strand invasion, a vital step of homologous recombination
  • functionally cooperates with RAD51AP1 to enhance the recombinase function of RAD51)
  • either directly or through an intermediary, such as RAD51, has a key role in the recruitment of RAD51AP1 to DNA damage
  • directly interacts with KEAP1, an oxidative stress sensor that binds and represses the master antioxidant transcription factor NFE2L2
  • regulates the rate of NFE2L2 export from the nucleus following induction
  • AMER1, PALB2, and SQSTM1 bind KEAP1 to activate NFE2L2
  • ability of phosphorylated RPA1 to stimulate fork recovery is mediated through the PALB2 tumor suppressor protein
  • PALB2 plays a critical role in DNA HR by recruiting BRCA2 and RAD51 to DNA breaks to initiate DNA repair
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCN
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation      
    c.1592delT, in familial breast cancer cases, truncating the protein, leading to little BRCA2-binding capacity and deficient in homologous recombination and crosslink repair
    tumoral germinal mutation     loss of function
    in patients with primary ovarian, fallopian tube, or peritoneal cancers
    Susceptibility
  • to breast cancer
  • to colorectal cancer (CRC)
  • Variant & Polymorphism other
  • truncating mutations increasing the risk of breast cancer, moderate-risk allele for breast cancer, founder mutations in Quebec and Finland
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    synthetic lethal therapeutic strategy for cancer treatment using PARP inhibitors
    ANIMAL & CELL MODELS