{"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":[],"notes":[],"symbol":"POLA1","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":[]},"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/"}]}}