DNA polymerase alpha (POLA1)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
The catalytic subunit of the polymerase alpha-primase complex, essential for replication initiation and Okazaki fragment synthesis; inhibition arrests S phase.
- 3 · How drugs use it
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.
External identifiers
Biology
The catalytic subunit of the polymerase alpha-primase complex, essential for replication initiation and Okazaki fragment synthesis; inhibition arrests S phase.
- All dividing cells
- Leukaemias and solid tumours treated with nucleoside analogues
Latest papers
topQuery 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.
Similar pages
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- Key paperBurris 1997: gemcitabine becomes the first standard treatment for advanced pancreatic cancer
- Key paperMPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer
- InstitutionMays Cancer Center at UT Health San Antonio
- Key paperConroy 2011: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer (PRODIGE 4/ACCORD 11)