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FLASH GENE
Symbol RAD51 contributors: shn/mct - updated : 25-10-2021
HGNC name RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)
HGNC id 9817
Corresponding disease
FANCR Fanconi anemia, complementation group R
MMVC2 congenital mirror movements, RAD51 related
Location 15q15.1      Physical location : 40.987.326 - 41.024.354
Synonym name
  • BRCA1/BRCA2-containing complex, subunit 5
  • RAD51 homolog protein
  • RecA-like protein
  • recombination protein A
  • RecA, E. coli, homolog of
  • DNA repair protein RAD51 homolog 1
    • Synonym symbol(s) RECA, RAD51A, HRAD51, HsRad51, HsT16930, RAD51L3, RAD51D, BRCC5, FANCR
    DNA
    TYPE functioning gene
    STRUCTURE 37.03 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • promoter is regulated by multiple factors, and that its expression is gradually activated as cells progress toward malignancy
    • MAPPING cloned Y linked N status confirmed
    Map cen - D15S994 - D15S968 - RAD51 - D15S641 - qter
    RNA
    TRANSCRIPTS type messenger
    text transcript variants utilizing alternative polyA signals exist
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 2299 - 339 - 2008 18417535
    10 splicing 2302 - 340 - 2008 18417535
    9 - 2177 - 280 - 2008 18417535
    10 - 2147 - 340 - 2008 18417535
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine   moderately
    Endocrineadrenal gland   highly
    Lymphoid/Immunespleen    
     thymus   moderately
    Reproductivefemale systemovary  moderately
     male systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  predominantly
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a putative nuclear localization signal (NLS)
  • two ATP binding domains
  • an helix hairpin-helix motif
  • a HhH domain
    • secondary structure two flexible loops, L1 and L2, proposed to be sites for DNA binding
    mono polymer homomer , heteromer , trimer , oligo
    HOMOLOGY
    interspecies ortholog to Rad51, Mus musculus
    ortholog to rad51, danio rerio
    ortholog to RAD51, Pan troglodytes
    intraspecies paralog to RAD51L1, RAD51C, RAD51L3, XRCC2 and XRCC3
    Homologene
    FAMILY
  • recA family
  • RAD51 subfamily
    • CATEGORY regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • colocalized with RPA1
  • condensed nuclear chromosome
  • colocalized with RAD51AP1 to multiple nuclear foci upon induction of DNA damage
  • XRCC2 and other HR proteins, including the key recombinase RAD51, co-localize with the centrosome
    • basic FUNCTION
  • involved in homologous recombination and DNA repair: forms a nucleoprotein filament on single-strand DNA regions and catalyses the search forhomologous sequences, strand paring and strand exchange
  • involved in immunoglobulin switch recombination
  • plays an essential role in the proliferation of cells
  • level of RAD51 is important for efficient restoration of replication forks by homologous recombination
  • key enzyme that functions in homologous recombination and recombinational repair of double strand breaks
  • acting as an ATPase
  • holoenzyme complex containing BRCA1, BRCA2, BARD1 and RAD51 act as an ubiquitin E3 ligase that enhances cellular survival following DNA damage
  • plays a parallel role in HR during the repair of DNA double-strand breaks (DSBs)
  • requires ATP for the catalysis of DNA strand exchange
  • play an important role in the repair of DNA double-strand breaks (DSBs) by homologous recombination
  • important new role in the oxidative stress response of human cells
  • protects newly synthesized DNA from MRE11-dependent degradation and promotes continuous DNA synthesis
  • RAD51 recombinase and the meiosis-specific DMC1 recombinase promote the formation of strand-invasion products (D-loops) between homologous molecules
  • key protein of homologous recombination, contributing to the DNA lesion bypass through its DNA strand invasion activity
  • in the context of ICL (interstrand cross-links) repair, RAD51 is loaded onto stalled replication forks before double-strand break formation
  • mediates homologous recombination by forming an active DNA nucleoprotein filament (NPF)
  • is important for restarting stalled replication forks and for repairing DNA double-strand breaks (DSBs) through a pathway called homology-directed repair (HDR)
  • low levels of mutant protein were sufficient for disruption of RAD51 activity and generation of chromosomal rearrangements
  • is a multifunctional protein that catalyzes recombination directly in mitosis and indirectly, via DMC1, during meiosis
  • EP400 and RAD51 are present in the same complex and both favor chromatin remodeling around DSBs
  • DMC1 dominance in promoting strand exchange between homologs involves repression of RAD51 strand-exchange activity
  • both RAD51 and DMC1 are required for interhomolog recombination during meiosis
  • may likely contribute to G2/M transition in embryonic stem cells, while preserving genomic integrity in global organization of DNA replication fork
  • catalyzes DNA pairing and strand exchange reactions that are central to homologous recombination and homology-directed DNA repair
  • RAD51 and DMC1 form partially overlapping co-foci
  • DMC1 and RAD51 are essential eukaryotic recombinases that mediate homologous chromosome pairing during homologous recombination
  • exhibits a slow kinetics of recruitment to DNA damage sites in aged fibroblasts
  • RAD51 negatively participated in autophagy
  • is the major eukaryotic HR repair protein
  • forms nucleoprotein filaments on 5prime–3prime resected single-stranded DNA and catalyzes homologous pairing and DNA strand invasion and exchange
  • having additional roles in interstrand crosslink (ICL) repair distinct from its recombinase function
    • CELLULAR PROCESS cell cycle
    nucleotide, recombination
    nucleotide, repair, recombination
    PHYSIOLOGICAL PROCESS
    text
  • DNA unwinding during replication
  • meiotic and mitotic recombination
  • positive regulation of DNA ligation
    • PATHWAY
    metabolism
    signaling
    may participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair
    a component
  • part of a complex with RAD51C and RAD51B
  • homo-oligomer
    • INTERACTION
    DNA binding to damaged DNA and single- or double-stranded DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • BRCA1,
  • BARD1, TP53
  • RAD54
  • SHFM1
  • XRCC3, RAD54L and RAD54B
  • RAD51AP1 and RAD51AP2
  • CHEK1/CHK1
  • interacting with the MND1-PSMC3IP heterodimer
  • interacting with OBFC2B
  • DNA helicase Srs2
  • SFPQ
  • important function of XRCC2 is to enhance the activity of RAD51, so that the loss of XRCC2 results in a severe delay in the early response of RAD51 to DNA damage
  • assembly of RAD51 at DNA damage is strictly controlled by RAD51 mediators, including BRCA1 and BRCA2
  • associates with RAD52, RAD54, and BRCA2 during recombinational repair
  • SFPQ association with the RAD51 protein complex is essential for homologous recombination repair of DNA damage and maintaining genome integrity
  • directly binds GEMIN2/SIP1
  • interacting with PALB2 (RAD51 interacted with the N terminus (AAs 1–200) of PALB2 and also its C terminus (residues 853–1186)
  • interacting with BRCA2 (role of BRCA2 in catalysing the delivery of RAD51 to sites of DNA damage)
  • in cooperation with RAD54 may have a new role in DNA lesion bypass that is distinct from DNA strand invasion
  • SWI5-SFR1 directly interacts with RAD51 and plays a critical role in homologous recombination repair
  • BRCA2 interacts with RAD51 through both the BRC repeats and the C-ter
  • BRCA2 specifically binds to RAD51 via eight BRC repeat motifs and delivers RAD51 to double-stranded DNA breaks
  • has an active role in homologous recombination (HR) and DNA double-strand break (DSB) repair but does not alter the intracellular level of the RAD51
  • CDK1 permits resection by phosphorylation of RBBP8 but also prevents RAD51 binding to the resected ends during M-phase double-strand break repair
  • RAD52 is potentially an alternative repair pathway of RAD51-mediated homologous recombination (HR)
  • MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination
  • SPIDR independently interacts with BLM and RAD51 and promotes the formation of a BLM/RAD51-containing complex of biological importance
  • interacts directly with the RAD51 paralogue complex BCDX2 and functions in parallel to the Fanconi anaemia pathway to promote efficient homologous recombination at damaged replication forks
  • ATRX stimulates RAD51-mediated DNA strand exchange and promotes branch migration of Holliday junctions
  • MEIOB appeared to be dispensable for the initial loading of recombinases but was required to maintain a proper number of RAD51 and DMC1 foci beyond the zygotene stage
  • FBXO18 binds directly to RAD51 and is able to disrupt RAD51 filaments on DNA through its ssDNA translocase function
  • AGO2 very likely functions directly in mediating RAD51 accumulation at DSBs
  • BRCA2, a key RAD51 binding partner, coordinates the activity of the central cell-cycle drivers CDKs and PLK1 to promote RAD51-mediated genome stability control
  • PSMC3IP-MND1 induces changes in the conformation of RAD51 that profoundly alter the basic properties of RAD51
  • BRCA2 facilitates nucleation of RAD51 filaments at multiple sites on single-stranded DNA
  • FBXO18 acting as a negative regulator of RAD51 function in human cells
  • ATM is needed for later steps in HR after RAD51 nucleofilament formation
  • DMC1 and RAD51 are conserved recombinases that catalyze homologous recombination
  • CSE1L associates with RAD51 in human cells, and negatively regulates the nuclear protein level of RAD51 under normal conditions
  • TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin
  • BRCA2 interacts directly with both RAD51 and DMC1 (pMID: 26976601)
  • NEK1 regulates RAD51 removal to orchestrate HR and replication fork stability.
  • by specifically regulating RAD51 activity at uncoupled replication forks, MMS22L-TONSL stabilizes perturbed replication forks by promoting replication fork reversal and stimulating their HR-mediated restart
  • NEK8 is required for efficient DNA damage-induced RAD51 foci formation
  • RECQL5 removes RAD51 filaments stabilizing stalled replication forks at common fragile sites (CFSs) and hence facilitates CFS cleavage by MUS81-EME1
  • both BRCA1 and BARD1 bind DNA and interact with RAD51, and BRCA1-BARD1 enhances the recombinase activity of RAD51
    • suggesting a sex-specific function for the two proteins)
  • SYCP3 functions in meiotic homologous recombination biased to interhomologous chromosomes, by regulating the strand invasion activities of the RAD51 and DMC1 recombinases
  • E2F7 restricts homologous recombination through the transcriptional repression of RAD51
  • the bromodomain of BRD9 binds acetylated K515 on ATRX and facilitates ATRX interaction with RAD51, which is essential for HR
  • BRME1 is a novel recombination factor and probably mediates DMC1/RAD51 recruitment to ssDNA or their stability on chromosomes through physical interaction with HSF2BP
  • prominent RPA1-interacting partners are the tumor suppressor protein TP53, RAD51, ATRIP and ETAA1
  • crucial role for TOPORS-mediated RAD51 SUMOylation in promoting Homologous recombination (HR) repair and genomic maintenance
    • cell & other
  • mtDNA is a novel RAD51 substrate and homologous recombination have an important role in the maintenance of the human mitochondrial genome
    • REGULATION
    activated by BRCA2
    BCR/ABL oncogenic tyrosine kinase
    BRCA4
    inhibited by RAD51 pathway, specifically inhibited by BCL2
    Phosphorylated by PLK1, that phosphorylates the essential RAD51 recombinase at serine 14 (S14) during the cell cycle and in response to DNA damage
    Other activity and level are regulated by p53
    intracellular level of RAD51 is affected by TGF_beta
    phosphorylated on Thr-309 by CHEK1/CHK1, may enhance association with chromatin at sites of DNA damage and promote DNA repair by homologous recombination
    regulated by ATR (ATR-dependent control of RAD51 contribute to ensure cellular recovery after DSB formation at stalled forks)
    phosphorylation of RAD51 Ser 192 in response to DNA damage controls RAD51 activity and DNA repair by homologous recombination
    down-regulation of RAD51 activity is important during meiosis to prevent RAD51 from competing with Dmc1 for repair of meiotic DSBs
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCR , MMVC2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in breast cancer with poor prognosis
    tumoral   LOH    
    in breast cancer
    tumoral     --over  
    in pancreatic adenocarcinoma
    tumoral     --over  
    in the majority of human cancers
    Susceptibility to breast cancer
    Variant & Polymorphism SNP 135G->C, increasing the risk of breast cancer in BRCA2 mutation carriers
    Candidate gene
  • overexpression of RAD51 in tumors can suppresse recombination defects and limits genomic instability during carcinogenic progression
    • Marker
    Therapy target
    ANIMAL & CELL MODELS
    mice heterozygous for a small deletion in the Rad51 gene are viable and fertile and homozygous Rad51 null mutation can be characterized as a preimplantational lethal mutation