======= DNA2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DNA2
  * **<color #00a2e8>Official Name</color>**: DNA replication helicase/nuclease 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1763|1763]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P51530|P51530]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DNA2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DNA2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601810|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the DNA2/NAM7 helicase family. The encoded protein is a conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. Mutations in this gene are associated with autosomal dominant progressive external ophthalmoplegia-6 (PEOA6) and Seckel syndrome 8. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double- strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)- dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function. {ECO:0000269|PubMed:16595799, ECO:0000269|PubMed:16595800, ECO:0000269|PubMed:18995831, ECO:0000269|PubMed:19487465, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:21572043, ECO:0000269|PubMed:22570407, ECO:0000269|PubMed:22570476}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|PDDEXK 1|
|Dna2|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|replication fork reversal|
|gamma DNA polymerase complex|
|site-specific endodeoxyribonuclease activity, specific for altered base|
|DNA replication, Okazaki fragment processing|
|mitotic telomere maintenance via semi-conservative replication|
|lagging strand elongation|
|DNA replication, removal of RNA primer|
|mitochondrial DNA repair|
|5-3 DNA helicase activity|
|G-quadruplex DNA unwinding|
|5-flap endonuclease activity|
|mitochondrial DNA metabolic process|
|mitochondrial DNA replication|
|t-circle formation|
|telomere maintenance via telomere trimming|
|formation of extrachromosomal circular DNA|
|nuclease activity|
|DNA replication checkpoint|
|single-stranded DNA helicase activity|
|DNA strand elongation involved in DNA replication|
|mitochondrial genome maintenance|
|DNA double-strand break processing|
|DNA strand elongation|
|telomere maintenance via semi-conservative replication|
|replication fork processing|
|helicase activity|
|positive regulation of DNA replication|
|base-excision repair|
|DNA-dependent DNA replication maintenance of fidelity|
|4 iron, 4 sulfur cluster binding|
|mitochondrial nucleoid|
|nuclear DNA replication|
|cell cycle DNA replication|
|DNA helicase activity|
|telomere maintenance|
|telomere organization|
|regulation of DNA replication|
|nuclear chromosome, telomeric region|
|DNA duplex unwinding|
|DNA geometric change|
|DNA-dependent DNA replication|
|DNA integrity checkpoint|
|regulation of signal transduction by p53 class mediator|
|double-strand break repair|
|cell cycle checkpoint|
|DNA replication|
|ATPase activity|
|RNA catabolic process|
|DNA conformation change|
|nucleic acid phosphodiester bond hydrolysis|
|anatomical structure homeostasis|
|nucleobase-containing compound catabolic process|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|mitochondrion organization|
|aromatic compound catabolic process|
|organic cyclic compound catabolic process|
|DNA repair|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|mitotic cell cycle|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|cellular homeostasis|
|cellular macromolecule catabolic process|
|cell cycle process|
|macromolecule catabolic process|
|chromosome organization|
|regulation of cell cycle|
|mitochondrion|
|cell cycle|
|RNA binding|
|DNA binding|
|ATP binding|
|homeostatic process|
|RNA metabolic process|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|-2.69|
|[[:results:exp518|RK-33 8μM R08 exp518]]|-2.25|
|[[:results:exp469|CFI-400945 25μM R08 exp469]]|-2.19|
|[[:results:exp329|Hydroxyurea 100μM R07 exp329]]|-2.19|
|[[:results:exp111|R-DABN 8μM R03 exp111]]|-2.13|
|[[:results:exp175|3-Bromopyruvate 7μM R04 exp175]]|-2.11|
|[[:results:exp524|Staurosporine 0.02μM R08 exp524]]|-2.02|
|[[:results:exp223|Cabazitaxel 0.001μM R05 exp223]]|-1.97|
|[[:results:exp350|Deferoxamine 11μM R07 exp350]]|-1.92|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|-1.92|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|-1.89|
|[[:results:exp342|Calcium Ionophore 0.4μM R07 exp342]]|-1.85|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|-1.85|
|[[:results:exp341|BRD2 inhibitor II 20μM R07 exp341]]|-1.81|
|[[:results:exp263|Aphidicolin 0.04μM R06 exp263]]|-1.74|
|[[:results:exp20|Etoposide 10μM R00 exp20]]|1.71|
|[[:results:exp225|Celastrol 0.12μM R05 exp225]]|1.86|
|[[:results:exp218|A-395 10μM R05 exp218]]|1.93|
|[[:results:exp475|CyclicAMP 200μM R08 exp475]]|2.16|
|[[:results:exp219|A-395N 10μM R05 exp219]]|2.54|
|[[:results:exp222|Betulinic acid 10 to 15μM on day4 R05 exp222]]|3.39|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: N/A
^Tissue^Fraction Of Cell Lines Where Essential^
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2121
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.36 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DNA2 Expression in NALM6 Cells: 6.36'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>