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First published online July 30, 2004
In this issue |
Point mutations can be repaired through targeted nucleotide exchange, in which the binding of an oligonucleotide specific for the target sequence leads to recruitment of cellular proteins and catalysis of nucleotide exchange. Transcription regulates targeted nucleotide exchange and, now, Erin Brachman and Eric Kmiec report that DNA replication also modulates this process in eukaryotes (see p. 3867). Previous studies indicated that transcriptionally active genes are more readily repaired by targeted nucleotide exchange than are non-expressed genes and that the untranscribed strand is corrected more efficiently. In prokaryotes, DNA replication also affects strand bias. To test whether this is also the case in eukaryotes, the authors constructed four SV40-genome-containing minichromosomes in which a mutant green fluorescent protein was incorporated on both sides of the SV40 origin of replication in both orientations. Using these constructs in COS-1 cells, the authors confirm the untranscribed strand repair bias and show that DNA replication increases this bias but only if the untranscribed strand is also the lagging strand in DNA synthesis.
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