PMID:16297932

Citation	Kouzminova, EA and Kuzminov, A (2006) Fragmentation of replicating chromosomes triggered by uracil in DNA. J. Mol. Biol. 355:20-33
Abstract	The dut mutants of Escherichia coli fail to hydrolyze dUTP and thus incorporate uracil into their DNA, suffering from chromosomal fragmentation. The postulated mechanism for the double-strand DNA breaks is clustered uracil excision, which requires high density of DNA-uracils. However, we did not find enough uracil residues or excision nicks in the DNA of dut mutants to account for clustered uracil excision. Using a dut recBC(Ts) mutant of E.coli to inquire into the mechanism of uracil-triggered chromosomal fragmentation, we show that this fragmentation requires DNA replication and, in turn, inhibits replication of the chromosomal terminus. As a result, origin-containing sub-chromosomal fragments accumulate in dut recBC conditions, indicating preferential demise of replication bubbles. We propose that the basic mechanism of the uracil-triggered chromosomal fragmentation is replication fork collapse at uracil-excision nicks. Possible explanations for the low level terminus fragmentation are also considered.
Links	PubMed Online version:10.1016/j.jmb.2005.10.044
Keywords	Base Sequence; Cell Nucleus Division; Chromosome Breakage; DNA/biosynthesis; DNA/chemistry; DNA/metabolism; DNA Replication; Escherichia coli/genetics; Exodeoxyribonuclease V/metabolism; Uracil/metabolism
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