Involvement of deoxycytidylate deaminase in the response to Sn1-type methylation DNA damage in budding yeast

R. Michael Liskay, Linda J. Wheeler, Christopher K. Mathews, Naz Erdeniz

Research output: Contribution to journalLetterpeer-review

3 Scopus citations

Abstract

In addition to spellchecking during DNA replication and modulating recombination, DNA mismatch repair (MMR) promotes cytotoxic responses to certain DNA-damaging agents [1]. In mammalian cells, the best-studied response is to Sn1-type methylating agents, including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [1]. Notably, MMR-deficient mammalian cells are resistant to the cytotoxic effects of these agents. A recent report showed that MMR deficiency conferred resistance to MNNG in yeast cells crippled for both homologous recombination (rad52Δ) and the detoxifying enzyme methylguanine methyltransferase (mgt1Δ) [2]. To better understand the response, we searched for additional genes modulating sensitivity to MNNG in rad52Δ mgt1Δ budding yeast. In addition to alleles of known MMR genes, we isolated an allele of DCD1 encoding the enzyme deoxycytidylate deaminase, which influences the dCTP:dTTP nucleotide pool ratio by catalyzing the conversion of dCMP to dUMP [3]. Models of the MMR-dependent cytotoxic response to Sn1-type methylating agents have included the incorporation of dTTP opposite O6-methyl guanine (O6metG) in the template [1]. Our findings lend further support to this aspect of the MMR-dependent response and highlight a mechanism for 'methylation' resistance that may be of therapeutic relevance for human cancer.

Original languageEnglish (US)
Pages (from-to)R755-R757
JournalCurrent Biology
Volume17
Issue number17
DOIs
StatePublished - Sep 4 2007

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

Fingerprint

Dive into the research topics of 'Involvement of deoxycytidylate deaminase in the response to Sn1-type methylation DNA damage in budding yeast'. Together they form a unique fingerprint.

Cite this