Blockade of Base Excision Repair

Inhibition of Small Lesions Results in Big Consequences to Cancer Cells

Carlo Vascotto, Melissa Fishel

Research output: Chapter in Book/Report/Conference proceedingChapter

6 Citations (Scopus)

Abstract

This chapter focuses on the base excision repair (BER) pathway which is responsible for the repair of single-base lesions and can be reconstituted in vitro with a glycosylase, AP endonuclease, polymerase β, and a ligase. BER is the predominant pathway for the repair of oxidative and alkylation DNA damage as well as a basic or baseless sites. Without this balance of enzymatic activities, incomplete processing of the damage occurs, repair intermediates accumulate, and eventually cells will die. Inhibition of proliferation and cell death are desirable in tumor cell populations, therefore inhibitors of BER proteins are under development and currently being evaluated in the clinic. Several of these agents are being evaluated in combination with numerous existing chemotherapeutic agents and radiation therapy. Combination therapy with agents that generate DNA damage that is repaired by BER is reasonable and demonstrating efficacy both preclinically and in early clinical trials.

Original languageEnglish
Title of host publicationDNA Repair in Cancer Therapy
PublisherElsevier Inc.
Pages29-53
Number of pages25
ISBN (Print)9780123849991
DOIs
StatePublished - 2012

Fingerprint

DNA Repair
DNA Damage
Neoplasms
DNA-(Apurinic or Apyrimidinic Site) Lyase
Alkylation
Ligases
Cell Death
Radiotherapy
Clinical Trials
Population
Proteins
Therapeutics

ASJC Scopus subject areas

  • Dentistry(all)
  • Medicine(all)

Cite this

Blockade of Base Excision Repair : Inhibition of Small Lesions Results in Big Consequences to Cancer Cells. / Vascotto, Carlo; Fishel, Melissa.

DNA Repair in Cancer Therapy. Elsevier Inc., 2012. p. 29-53.

Research output: Chapter in Book/Report/Conference proceedingChapter

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