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FLASH GENE
Symbol RAD50 contributors: mct/pgu - updated : 31-01-2013
HGNC name RAD50 homolog (S. cerevisiae)
HGNC id 9816
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • SMC N-terminal ATP binding domain
  • central heptad repeat domain
  • zinc hook domain mediating zinc-dependent intercomplex associations of MRN (MRE11-RAD50-NBS1), which is important for DNA tethering
    • HOMOLOGY
    interspecies homolog to yeast S.cerevisiae RAD50
    Homologene
    FAMILY
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,telomere
    basic FUNCTION
  • involved in DNA double-strand break repair by end joining (non homologous recombination) and meiosis specific double strand break formation
  • essential for cell growth and viability
  • having a biological role as an early participant in cellular DNA-damage responses
  • role of MRN in the maintenance of genome stability through preventing rereplication and rereplication-associated double-stranded breaks when licensing control is compromised
  • MRE11A/RAD50/NBS1 (MRN) complex has a central function in facilitating activation of the ATM protein kinase at sites of DNA double-strand breaks (DSBs)
  • phosphorylation of RAD50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity
  • functions of MRE11 complex are integrated by the coiled coils of RAD50
  • ATP hydrolysis opens the RAD50-MRE11A complex, and MRE11A maintains exonuclease activity
    • CELLULAR PROCESS nucleotide, repair, recombination
    nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with MRE11A and NBN, exonuclease 3' to 5' and endonuclease activities and with BLM (complex MRE11A, RAD50 and NBN (MRN), are central to maintaining genomic stability)
  • MR complex contains the MRE11A nuclease dimer and two flanking RAD50 ATPase domains
    • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
    ATP
    protein
  • BLM, WRN, MRE11A, NBN
  • interaction with RAD50, XRS2/NBN, complex required for TERF1 phosphorylation by ATM and such phosphorylation results in the release of TERF1 from telomeres, promoting telomerase access to the ends of telomeres
  • interacting with NBN in a stable complex, in absence of MRE11
  • NCL interacts with RAD50 via its arginine-glycine rich domain and is recruited to DSBs rapidly in an MRE11-NBS1-RAD50 complex-dependent manner
  • BRCA1 and BLM interact with RAD50 predominantly in S- and G2-phases, respectively
    • cell & other
    REGULATION
    Phosphorylated by ATM, that phosphorylates RAD50 at a single site (Ser-635) that plays an important adaptor role in signaling for cell cycle control and DNA repair
    ASSOCIATED DISORDERS
    corresponding disease(s) NBSLD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in microsatellite stable (MSS) colorectal cancers
    tumoral germinal mutation     loss of function
    in patients with primary ovarian, fallopian tube, or peritoneal cancers
    tumoral     --over  
    in melanoma cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS