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FLASH GENE
Symbol DNA2 contributors: mct/pgu - updated : 17-11-2016
HGNC name DNA replication helicase 2 homolog (yeast)
HGNC id 2939
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly Homo sapiensAdultmRNA
Digestivemouthtongue  highly
Lymphoid/Immunelymph node   highly
 thymus   highly
Nervousbrain   highly Homo sapiensAdultmRNA
 brainhindbraincerebellum highly Homo sapiensAdultmRNA
Urinarykidney   highly Homo sapiensAdultmRNA
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Muscularstriatumskeletal moderately Homo sapiensAdultmRNA
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal domain with potential roles in the maintenance of genomic stability
  • a potential Fe-S cluster domain, spanning the nuclease active site
  • conserved nuclease, ATPase, and helicase domains
  • HOMOLOGY
    interspecies homolog to yeast DNA2 (DNA replication helicase)
    homolog to murine Dna2 (79.9pc)
    homolog to rattus Dna2 (80.1pc)
    Homologene
    FAMILY
  • DNA2/NAM7 helicase family
  • CATEGORY enzyme , DNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • participates in both nuclear and mitochondrial DNA maintenance
  • interacting with DNA polymerase gamma and stimulating its activity
  • endonuclease/helicase participatING in eukaryotic DNA transactions including cleavage of long flaps generated during Okazaki fragment processing
  • having a nuclease activity that does not require, and in fact can create, 5prime single-stranded DNA ends
  • potential cross-talk between DNA2- and EXO1-dependent resection pathways
  • processing intermediate 5' flap structures occuring in DNA replication long-patch base excision repair in mitochondria
  • in mitochondria, participates in the removal of RNA primers during mtDNA replication
  • critical for long-patch base-excision repair (LP-BER), the predominant pathway for repairing small DNA lesions induced by oxidation, alkylation, and spontaneous hydrolysis
  • plays a role in DNA replication that is distinct from FEN1 and Okazaki fragment maturation
  • DNA2 cleavage of regressed nascent strands prevents fork reversal and thus stabilizes stalled forks to maintain genome stability during replication stress
  • multitasking protein involved in DNA replication and recombinational repair, and it is important for preservation of genomic stability
  • may represent a new mediator of the interplay between homology-directed repair (HDR)and the Fanconi anemia/BRCA pathway
  • shows partial redundancy for the replication checkpoint with checkpoint initiators RAD9-RAD1-HUS1
  • DNA2 reduces replication stress at telomeres, thereby preserving genome stability and suppressing cancer development, and that this may involve, at least in part, nucleolytic processing of telomeric G4
  • functions as both a helicase and a nuclease and plays a role in DNA repair and replication
  • DNA2-mediated resection is a major mechanism for the repair of DSBs with 5prime adducts
  • DNA2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component BLM-DNA2-RPA-NBN and EXO1-BLM-RPA-NBN constitute two DNA end resection machineries for human DNA break repair
    INTERACTION
    DNA binding
    RNA
    small molecule nucleotide,
  • ATP binding
  • protein
  • with FEN1, DNA2 is thought to be involved in the repair of oxidative lesions in DNA molecules
  • interacts with POLG and stimulates its catalytic activity
  • DNA2 associates with the replisome protein WDHD1 in a cell cycle-dependent manner
  • ATR pathway targets the DNA2 nuclease to process stalled forks and counteract fork reversal
  • DNA2 interacts with FANCD2, and cisplatin induces FANCD2 ubiquitylation even in the absence of DNA2
  • WRN and DNA2 interact physically and coordinate their enzymatic activities to mediate 5'-3' DNA end resection in a reaction dependent on RPA1
  • WRN and BLM act epistatically with DNA2 to promote the long-range resection of double strand break ends in human cells
  • multifaceted role of the TOP3A-RMI1-RMI2 ensemble and of DNA2 in the DNA resection reaction
  • DNA2 nuclease and WRN ATPase activities functionally interact to degrade reversed replication forks and promote replication restart, thus preventing aberrant processing of unresolved replication intermediates
  • RECQL limits DNA2 activity by preventing extensive nascent strand degradation
  • flexibly-tethered DNA2-RPA1 interaction that recruits DNA2 to RPA1-coated DNA
  • DNA2 motor promotes the enzyme capacity to degrade dsDNA in conjunction with BLM or WRN and thus promote the repair of broken DNA
  • WRN participates in one of the two alternative long-range resection pathways mediated by DNA2 or EXO1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PEOA6 , SCKL8
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in adult-onset disorders of mtDNA maintenance
    tumoral somatic mutation      
    mutations in DNA2, found in estrogen-dependent cancers, are clustered in the helicase and nuclease domains, suggesting activity impairment
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • appropriate candidate for molecular screening in subjects with sporadic or familial PEO with ascertained instability of muscle mtDNA
  • Marker
    Therapy target
    ANIMAL & CELL MODELS