Methylation of deoxycytidine incorporated by excision-repair synthesis of DNA

Michael B. Kastan, Bonnie J. Gowans, Michael W. Lieberman

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Methylation of deoxycytidine incorporated by DNA excision-repair was studied in human diploid fibroblasts following damage with ultraviolet radiation, N-methyl-N-nitrosourea, or N-acetoxy-2-acetylami-nofluorene. In confluent, nondividing cells, methylation in repair patches induced by all three agents is slow and incomplete. Whereas after DNA replication in logarithmic-phase cultures a steady state level of 3.4% 5-methylcytosine is reached in less than 2 hr after cells are labeled with 6-3H-deoxycytidine, following ultraviolet-stimulated repair synthesis in confluent cells it takes about 3 days to reach a level of ∼2.0% 5-methylcytosine in the repair patch. In cells from cultures in logarithmic-phase growth, 5-methylcytosine formation in ultraviolet-induced repair patches occurs faster and to a greater extent, reaching a level of ∼2.7% in 10-20 hr. Preexisting hypomethylated repair patches in confluent cells are methylated further when the cells are stimulated to divide; however, the repair patch may still not be fully methylated before cell division occurs. Thus DNA damage and repair may lead to heritable loss of methylation at some sites.

Original languageEnglish (US)
Pages (from-to)509-516
Number of pages8
JournalCell
Volume30
Issue number2
DOIs
StatePublished - Sep 1982

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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