A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair

Lajos Haracska, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The human Y-family DNA polymerases, Polι, Polη, and Polκ, function in promoting replication through DNA lesions. However, because of their low fidelity, any involvement of these polymerases in DNA synthesis during base excision repair (BER) would be highly mutagenic. Mechanisms, therefore, must exist to exclude their participation in BER. Here, we show that although Polι, Polη, and Polκ are all able to form a covalent Schiff base intermediate with the 5′-deoxyribose phosphate (5′-dRP) residue that results from the incision of DNA at an abasic site by an AP endonuclease, they all lack the ability for the subsequent catalytic removal of the 5′-dRP group. Instead, the covalent trapping of these polymerases by the 5′-dRP residue inhibits their DNA synthetic activity during BER. The unprecedented ability of these polymerases for robust Schiff base formation without the release of the 5′-dRP product provides a means of preventing their participation in the DNA synthetic step of BER, thereby avoiding the high incidence of mutagenesis and carcinogenesis that would otherwise occur.

Original languageEnglish (US)
Pages (from-to)2777-2785
Number of pages9
JournalGenes and Development
Volume17
Issue number22
DOIs
StatePublished - Nov 15 2003

Fingerprint

Deoxyribose
DNA-Directed DNA Polymerase
DNA Repair
Phosphates
Schiff Bases
DNA
DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA Replication
Mutagenesis
Carcinogenesis
Incidence

Keywords

  • 5′-doexyribose phosphate
  • 5′-dRP lyase
  • Abasic site
  • Base excision repair
  • Y-family DNA polymerases

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. / Haracska, Lajos; Prakash, Louise; Prakash, Satya.

In: Genes and Development, Vol. 17, No. 22, 15.11.2003, p. 2777-2785.

Research output: Contribution to journalArticle

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