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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
Corresponding disease
PEOA6 progressive external ophthalmoplegia with mitochondrial DNA deletions 6
SCKL8 Seckel syndrome-8
Location 10q21.3      Physical location : 70.173.821 - 70.231.879
Synonym name
  • DNA replication ATP-dependent helicase-like homolog
  • DNA2-like helicase
    • Synonym symbol(s) KIAA0083, DN2L, FLJ10063, DNA2L, MGC133297
    EC.number 3.6.4.12
    DNA
    TYPE functioning gene
    STRUCTURE 57.91 kb     21 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 4416 - 1146 - 2009 19487465
    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