{"entity":{"id":"pola1","kind":"target","name":"DNA polymerase alpha (POLA1)","aka":[],"tldr":"DNA polymerase alpha starts every new DNA strand; nucleoside chemotherapies such as cytarabine, fludarabine and gemcitabine are converted inside cells into fake building blocks that jam this and the other replicative polymerases.","summary":"DNA polymerase alpha, with its primase partner, lays down the first stretch of every new DNA strand before polymerases delta and epsilon take over. The replicative polymerases are the shared target of the nucleoside analogues: cytarabine and fludarabine in leukaemia and gemcitabine in pancreatic, lung, bladder and breast cancer are phosphorylated inside cells into triphosphates that compete with natural nucleotides, are incorporated into DNA and stall the polymerase, ending chain growth and triggering cell death. Clofarabine and nelarabine work the same way in acute lymphoblastic leukaemia.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DNA_polymerase_alpha","links":[{"label":"UniProt P09884: POLA1","url":"https://www.uniprot.org/uniprotkb/P09884/entry"},{"label":"HGNC:9173 POLA1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9173"},{"label":"ChEMBL target CHEMBL2363042","url":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL2363042"}],"tags":["chembl-gap"],"related":["rrm1"],"cancers":["aml","all-leukemia","pancreatic","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["cytarabine","fludarabine","gemcitabine","clofarabine","nelarabine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"POLA1","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA lists POLA1 among essential proteins and finds the RNA at low tissue specificity; the 5 medicines aimed at it (Cytarabine, Fludarabine, Gemcitabine and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA POLA1: RNA low tissue specificity; high antibody staining in 15 normal tissues; highest cancer staining lymphoma (12 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Pancreatic ductal adenocarcinoma, Lung cancer (all types)); Open Targets associates it with 10 specific cancer types at or above 0.5 (acute lymphoblastic leukemia, non-small cell lung carcinoma, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, exocrine pancreatic carcinoma, ovarian carcinoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas POLA1 tissue","url":"https://www.proteinatlas.org/ENSG00000101868-POLA1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000101868 associations","url":"https://platform.opentargets.org/target/ENSG00000101868/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9173","ensembl":"ENSG00000101868","uniprot":"P09884","entrez":"5422","firstDescribed":1988,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Wong S.W. et al, EMBO J, 1988, \"Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3359994/","biology":"The catalytic subunit of the polymerase alpha-primase complex, essential for replication initiation and Okazaki fragment synthesis; inhibition arrests S phase.","whereFound":["All dividing cells","Leukaemias and solid tumours treated with nucleoside analogues"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"Housekeeping enzyme present in every dividing cell (DNA strand initiation); not a selection marker, which is why these drugs are given by cancer type rather than by test."}]},"route":"/targets/pola1/","neighbours":{"target":[{"id":"rrm1","kind":"target","name":"Ribonucleotide reductase (RRM1)","route":"/targets/rrm1/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"clofarabine","kind":"drug","name":"Clofarabine","route":"/drugs/clofarabine/"},{"id":"cytarabine","kind":"drug","name":"Cytarabine","route":"/drugs/cytarabine/"},{"id":"fludarabine","kind":"drug","name":"Fludarabine","route":"/drugs/fludarabine/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"nelarabine","kind":"drug","name":"Nelarabine","route":"/drugs/nelarabine/"}]}}