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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.
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.
In plain words · 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.
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.
The catalytic subunit of the polymerase alpha-primase complex, essential for replication initiation and Okazaki fragment synthesis; inhibition arrests S phase.
No product in this corpus aims at DNA polymerase alpha (POLA1) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
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.)
Sources: Human Protein Atlas POLA1 tissue; Open Targets ENSG00000101868 associations
First described 1988. 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". Source.
The catalytic subunit of the polymerase alpha-primase complex, essential for replication initiation and Okazaki fragment synthesis; inhibition arrests S phase.
RNA: low tissue specificity, detected in many normal tissues.
Medium: Caudate, Cerebral cortex, Endometrium, Epididymis, Gallbladder, Hippocampus, Kidney, Lung.
Medium only: carcinoid, prostate cancer, renal cancer.
HPA POLA1 tissue · HPA POLA1 pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | 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. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"DNA polymerase alpha" OR ABSTRACT:"DNA polymerase alpha" OR TITLE:"POLA1" OR ABSTRACT:"POLA1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DNA polymerase alpha (POLA1), not a curated reading list.
Shares Clofarabine, Fludarabine, Acute myeloid leukaemia.
Shares Clofarabine, Cytarabine, Acute myeloid leukaemia.
Shares Fludarabine, Cytarabine, Acute myeloid leukaemia.
Shares Ribonucleotide reductase (RRM1), Acute myeloid leukaemia.
Shares Fludarabine, Cytarabine, Acute myeloid leukaemia.
Shares Clofarabine, Cytarabine, Acute lymphoblastic leukaemia.
Shares Fludarabine, Cytarabine, Acute myeloid leukaemia.
Shares Nelarabine, Acute lymphoblastic leukaemia.