Family A and B DNA polymerases in cancer: Opportunities for therapeutic interventions

Vinit Shanbhag, Shrikesh Sachdev, Jacqueline A. Flores, Mukund J. Modak, Kamalendra Singh

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

DNA polymerases are essential for genome replication, DNA repair and translesion DNA synthesis (TLS). Broadly, these enzymes belong to two groups: replicative and non-replicative DNA polymerases. A considerable body of data suggests that both groups of DNA polymerases are associated with cancer. Many mutations in cancer cells are either the result of error-prone DNA synthesis by non-replicative polymerases, or the inability of replicative DNA polymerases to proofread mismatched nucleotides due to mutations in 3′-5′ exonuclease activity. Moreover, non-replicative, TLS-capable DNA polymerases can negatively impact cancer treatment by synthesizing DNA past lesions generated from treatments such as cisplatin, oxaliplatin, etoposide, bleomycin, and radiotherapy. Hence, the inhibition of DNA polymerases in tumor cells has the potential to enhance treatment outcomes. Here, we review the association of DNA polymerases in cancer from the A and B families, which participate in lesion bypass, and conduct gene replication. We also discuss possible therapeutic interventions that could be used to maneuver the role of these enzymes in tumorigenesis.

Original languageEnglish (US)
Article number5
JournalBiology
Volume7
Issue number1
DOIs
StatePublished - Mar 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • 30-50 exonuclease
  • Base excision repair
  • Cancer
  • DNA polymerase
  • DNA polymerase and cancer
  • Mismatch repair
  • Replication fork
  • Therapy for mismatch repair deficient cancers
  • Translesion DNA synthesis

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