TY - JOUR
T1 - Methylation of deoxycytidine incorporated by excision-repair synthesis of DNA
AU - Kastan, Michael B.
AU - Gowans, Bonnie J.
AU - Lieberman, Michael W.
N1 - Funding Information:
We thank Steven M. Cohn, Steven L. Dresler, Joseph W. Hoffmann, Dare1 J. Hunting and Bruce Ft. Krawisz for their thoughtful comments. This work was supported by grants from the National Cancer Institute and by Brown 8 Williamson Tobacco Corporation, Philip Morris Incorporated, R J. Reynolds Tobacco Company and United States Tobacco Company. M. B. K. is a trainee of the Medical Scientist Training Program Grant from the National Institute of General and Medical Sciences. Media were provided by the Washington University Cancer Center, which is supported by the National Cancer Institute.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1982/9
Y1 - 1982/9
N2 - 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.
AB - 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.
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U2 - 10.1016/0092-8674(82)90248-3
DO - 10.1016/0092-8674(82)90248-3
M3 - Article
C2 - 7139710
AN - SCOPUS:0020181396
VL - 30
SP - 509
EP - 516
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -