TY - JOUR
T1 - The Saccharomyces cerevisiae Helicase Rrm3p Facilitates Replication Past Nonhistone Protein-DNA Complexes
AU - Ivessa, Andreas S.
AU - Lenzmeier, Brian A.
AU - Bessler, Jessica B.
AU - Goudsouzian, Lara K.
AU - Schnakenberg, Sandra L.
AU - Zakian, Virginia A.
N1 - Funding Information:
V.A.Z. dedicates this paper to the memory of J.K. McDougall, whose work first introduced her to fragile sites. We thank J. Diffley for the Rad53p antibody, A. Pellicioli and M. Foiani for invaluable advice on detecting Rad53p phosphorylation, M. Paule for advice on tRNA transcription, E. Monson for help with chromosome loss assays, J. Rine, L. Rusche, B. Winsor, and S. Clark for strains and plasmids, and J. Broach and members of our lab for comments on the manuscript. We thank the National Institutes of Health (R37 GM26938), American Cancer Society (#PF00-013-01GMC, B.A.L.), NJ Commission on Cancer Research (J.B.B.), Austrian NSF, and the Leukemia and Lymphoma Society (A.S.I.) for financial support.
PY - 2003/12
Y1 - 2003/12
N2 - The Saccharomyces cerevisiae RRM3 gene encodes a 5′ to 3′ DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Δ cells, especially at low temperatures. Each site whose replication was affected by Rrm3p is assembled into a nonnucleosomal protein-DNA complex. At tRNA genes and the silent mating type loci, disruption of these complexes eliminated dependence upon Rrm3p. These data indicate that the Rrm3p DNA helicase helps replication forks traverse protein-DNA complexes, naturally occurring impediments that are encountered in each S phase.
AB - The Saccharomyces cerevisiae RRM3 gene encodes a 5′ to 3′ DNA helicase. While replication of most of the yeast genome was not dependent upon Rrm3p, in its absence, replication forks paused and often broke at an estimated 1400 discrete sites, including tRNA genes, centromeres, inactive replication origins, and transcriptional silencers. These replication defects were associated with activation of the intra-S phase checkpoint. Activation of the checkpoint was critical for viability of rrm3Δ cells, especially at low temperatures. Each site whose replication was affected by Rrm3p is assembled into a nonnucleosomal protein-DNA complex. At tRNA genes and the silent mating type loci, disruption of these complexes eliminated dependence upon Rrm3p. These data indicate that the Rrm3p DNA helicase helps replication forks traverse protein-DNA complexes, naturally occurring impediments that are encountered in each S phase.
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U2 - 10.1016/S1097-2765(03)00456-8
DO - 10.1016/S1097-2765(03)00456-8
M3 - Article
C2 - 14690605
AN - SCOPUS:0348047594
SN - 1097-2765
VL - 12
SP - 1525
EP - 1536
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -