POLD1 [The Human Chemical-Genetic Interaction Map Project]

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======= POLD1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: POLD1
  * **<color #00a2e8>Official Name</color>**: DNA polymerase delta 1, catalytic subunit
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5424|5424]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P28340|P28340]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=POLD1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20POLD1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/174761|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**:  As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611}.

<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'>
|DNA pol B exo1|
|DNA pol B|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|DNA replication proofreading|
|3-5-exodeoxyribonuclease activity|
|delta DNA polymerase complex|
|base-excision repair, gap-filling|
|nucleotide-excision repair complex|
|fatty acid homeostasis|
|nucleotide-excision repair, DNA gap filling|
|telomere maintenance via semi-conservative replication|
|DNA-directed DNA polymerase activity|
|mismatch repair|
|nucleotide-excision repair, DNA incision, 5-to lesion|
|base-excision repair|
|DNA damage response, detection of DNA damage|
|DNA-dependent DNA replication maintenance of fidelity|
|nucleotide-excision repair, DNA incision|
|translesion synthesis|
|4 iron, 4 sulfur cluster binding|
|aggresome|
|nuclear DNA replication|
|cell cycle DNA replication|
|DNA synthesis involved in DNA repair|
|postreplication repair|
|damaged DNA binding|
|anion homeostasis|
|nucleotide binding|
|transcription-coupled nucleotide-excision repair|
|cellular response to UV|
|telomere maintenance|
|telomere organization|
|nuclear chromosome, telomeric region|
|DNA biosynthetic process|
|nucleotide-excision repair|
|cellular response to light stimulus|
|DNA-dependent DNA replication|
|lipid homeostasis|
|response to UV|
|cellular response to radiation|
|DNA replication|
|nucleic acid phosphodiester bond hydrolysis|
|response to light stimulus|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|anatomical structure homeostasis|
|chromatin binding|
|response to radiation|
|DNA repair|
|detection of stimulus|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|ion homeostasis|
|cellular homeostasis|
|cell cycle process|
|chromosome organization|
|nucleobase-containing compound biosynthetic process|
|chemical homeostasis|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|organic cyclic compound biosynthetic process|
|cell cycle|
|DNA binding|
|cellular nitrogen compound biosynthetic process|
|homeostatic process|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|macromolecule biosynthetic process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' 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:exp80|RO-3307 4.7μM R02 exp80]]|-2|
|[[:results:exp49|NFN1 0.1μM R01 exp49]]|1.7|
|[[:results:exp41|BI-2536 0.001μM R01 exp41]]|1.76|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:c:cdc73|CDC73]]|0.5|
|[[:human genes:d:dock6|DOCK6]]|0.495|
|[[:human genes:p:psmd3|PSMD3]]|0.478|
|[[:human genes:s:sh3bp1|SH3BP1]]|0.448|
|[[:human genes:g:golga6l1|GOLGA6L1]]|0.446|
|[[:human genes:t:tyms|TYMS]]|0.44|
|[[:human genes:c:cope|COPE]]|0.438|
|[[:human genes:c:cgb2|CGB2]]|0.437|
|[[:human genes:c:cdca3|CDCA3]]|0.436|
|[[:human genes:c:cdh24|CDH24]]|0.433|
|[[:human genes:t:tceb3c|TCEB3C]]|0.433|
|[[:human genes:t:tceb3cl|TCEB3CL]]|0.432|
|[[:human genes:p:psmd7|PSMD7]]|0.429|
|[[:human genes:c:cnot1|CNOT1]]|0.428|
|[[:human genes:p:psmb2|PSMB2]]|0.427|
|[[:human genes:t:tbc1d3h|TBC1D3H]]|0.424|
|[[:human genes:p:psmb4|PSMB4]]|0.422|
|[[:human genes:w:wdr75|WDR75]]|0.418|
|[[:human genes:r:rrp1|RRP1]]|0.415|
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.415|
|[[:human genes:s:sec13|SEC13]]|0.414|
|[[:human genes:x:xylt2|XYLT2]]|0.413|
|[[:human genes:a:acbd4|ACBD4]]|0.413|
|[[:human genes:t:ticrr|TICRR]]|0.412|
|[[:human genes:p:psmc5|PSMC5]]|0.412|
|[[:human genes:p:psma6|PSMA6]]|0.412|
|[[:human genes:r:rrn3|RRN3]]|0.411|
|[[:human genes:p:plekha4|PLEKHA4]]|0.408|
|[[:human genes:r:rplp1|RPLP1]]|0.407|
|[[:human genes:s:supt5h|SUPT5H]]|0.406|
|[[:human genes:p:polr2a|POLR2A]]|0.405|
|[[:human genes:a:aqr|AQR]]|0.405|
|[[:human genes:p:pla2g4f|PLA2G4F]]|0.404|
|[[:human genes:p:psmc1|PSMC1]]|0.402|
|[[:human genes:c:cmya5|CMYA5]]|0.401|
|[[:human genes:d:dtl|DTL]]|0.401|
|[[:human genes:g:gon4l|GON4L]]|0.401|
|[[:human genes:c:ccna2|CCNA2]]|0.401|
|[[:human genes:t:tbc1d3c|TBC1D3C]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 621/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|23/28|
|blood|20/28|
|bone|25/26|
|breast|31/33|
|central nervous system|51/56|
|cervix|4/4|
|colorectal|12/17|
|esophagus|10/13|
|fibroblast|1/1|
|gastric|13/16|
|kidney|17/21|
|liver|16/20|
|lung|62/75|
|lymphocyte|14/16|
|ovary|22/26|
|pancreas|22/24|
|peripheral nervous system|16/16|
|plasma cell|14/15|
|prostate|0/1|
|skin|17/24|
|soft tissue|8/9|
|thyroid|2/2|
|upper aerodigestive|14/22|
|urinary tract|26/29|
|uterus|5/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 779
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.24 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='POLD1 Expression in NALM6 Cells: 7.24'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>