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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	57.91 kb     21 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001080449 21 - 4416 NP_001073918 - 1146 - 2009 19487465

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Adult mRNA Digestive mouth tongue     highly Lymphoid/Immune lymph node       highly   thymus       highly Nervous brain       highly Homo sapiens Adult mRNA   brain hindbrain cerebellum   highly Homo sapiens Adult mRNA Urinary kidney       highly Homo sapiens Adult mRNA

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Muscular striatum skeletal   moderately Homo sapiens Adult mRNA

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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