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Journal of Bacteriology, January 1999, p. 477-482, Vol. 181, No. 2
Department of Biology and Rosenstiel Basic
Medical Sciences Research Center, Brandeis University, Waltham,
Massachusetts 02454-9110
Received 5 August 1998/Accepted 11 November 1998
Misalignment of repeated sequences during DNA replication can lead
to deletions or duplications in genomic DNA. In Escherichia coli, such genetic rearrangements can occur at high frequencies, independent of the RecA-homologous recombination protein, and are sometimes associated with sister chromosome exchange (SCE). Two
mechanisms for RecA-independent genetic rearrangements have been
proposed: simple replication misalignment of the nascent strand and its
template and SCE-associated misalignment involving both nascent
strands. We examined the influence of the 3' exonuclease of DNA
polymerase III and exonuclease I on deletion via these mechanisms in
vivo. Because mutations in these exonucleases stimulate tandem repeat
deletion, we conclude that displaced 3' ends are a common intermediate
in both mechanisms of slipped misalignments. Our results also confirm
the notion that two distinct mechanisms contribute to slipped
misalignments: simple replication misalignment events are sensitive to
DNA polymerase III exonuclease, whereas SCE-associated events are
sensitive to exonuclease I. If heterologies are present between
repeated sequences, the mismatch repair system dependent on MutS and
MutH aborts potential deletion events via both mechanisms. Our results
suggest that simple slipped misalignment and SCE-associated
misalignment intermediates are similarly susceptible to
destruction by the mismatch repair system.
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Slipped Misalignment Mechanisms of Deletion
Formation: In Vivo Susceptibility to Nucleases
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Corresponding author. Mailing address: Rosenstiel Basic
Medical Sciences Research Center MS029, Brandeis University, Waltham, MA 02454-9110. Phone: (781) 736-2497. Fax: (781) 736-2405. E-mail: lovett{at}hydra.rose.brandeis.edu.
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