DOI: 10.1126/science.1083964. Uncoupling of Leading- and Lagging-Strand DNA Replication During Lesion Bypass in Vivo

Uncoupling of Leading- and Lagging-Strand DNA Replication During Lesion Bypass in Vivo

10.1126/science.1083964

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Numerous agents attack DNA, forming lesions that impair normal replication. Specialized DNA polymerases transiently replace the replicative polymerase and copy past lesions, thus generating mutations, the major initiating cause of cancer. We monitored, in Escherichia coli , the kinetics of replication of both strands of DNA molecules containing a single replication block in either the leading or lagging strand. Despite a block in the leading strand, lagging-strand synthesis proceeded further, implying transient uncoupling of concurrent strand synthesis. Replication through the lesion requires specialized DNA polymerases and is achieved with similar kinetics and efficiencies in both strands.

Bibliography

PageÌs, V., & Fuchs, R. P. (2003). Uncoupling of Leading- and Lagging-Strand DNA Replication During Lesion Bypass in Vivo. Science, 300(5623), 1300â1303.

Authors 2

Vincent Pagès (first)
Robert P. Fuchs (additional)

References 23 Referenced 171

W. D. Rupp, P. Howard-Flanders, J. Mol. Biol.31, 291 (1968). (10.1016/0022-2836(68)90445-2) / J. Mol. Biol. (1968)
M. Cordeiro-Stone, R. I. Schumacher, R. Meneghini, Biophys. J.27, 287 (1979). (10.1016/S0006-3495(79)85218-2) / Biophys. J. (1979)
J.-I. Tomizawa, Y. Sakakibara, T. Kakfuda, Proc. Natl. Acad. Sci. U.S.A.71, 2260 (1974). (10.1073/pnas.71.6.2260) / Proc. Natl. Acad. Sci. U.S.A. (1974)
Materials and methods are available as supporting material on Science Online.
G. R. Hoffmann, R. P. P. Fuchs, Chem. Res. Toxicol.10, 347 (1997). (10.1021/tx960128n) / Chem. Res. Toxicol. (1997)
J. A. Miller, Cancer Res.30, 559 (1970). / Cancer Res. (1970)
10.1093/emboj/19.22.6259
V. Pagès R. P. Fuchs unpublished data.
R. P. P. Fuchs, N. Schwartz, M. P. Daune, Nature294, 657 (1981). (10.1038/294657a0) / Nature (1981)
M. Seigneur, V. Bidnenko, S. D. Ehrlich, B. Michel, Cell95, 419 (1998). (10.1016/S0092-8674(00)81772-9) / Cell (1998)
10.1126/science.1081328
P. McGlynn, R. G. Lloyd, K. J. Marians, Proc. Natl. Acad. Sci. U.S.A.98, 8235 (2001). (10.1073/pnas.121007798) / Proc. Natl. Acad. Sci. U.S.A. (2001)
N. P. Higgins, K. Kato, B. Strauss, J. Mol. Biol.101, 417 (1976). (10.1016/0022-2836(76)90156-X) / J. Mol. Biol. (1976)
S. Prakash, L. Prakash, Genes Dev.16, 1872 (2002). (10.1101/gad.1009802) / Genes Dev. (2002)
J. Wagner, H. Etienne, R. Janel-Bintz, R. P. P. Fuchs, DNA Repair1, 159 (2002). (10.1016/S1568-7864(01)00012-X) / DNA Repair (2002)
V. Pagès, R. P. Fuchs, Oncogene21, 8957 (2002). (10.1038/sj.onc.1206006) / Oncogene (2002)
A. Bresson, R. P. Fuchs, EMBO J.21, 3881 (2002). (10.1093/emboj/cdf363) / EMBO J. (2002)
10.1126/science.1070236
M. F. Goodman, B. Tippin, Nature Rev. Mol. Cell Biol.1, 101 (2000). / Nature Rev. Mol. Cell Biol. (2000)
M. D. Sutton, G. C. Walker, Proc. Natl. Acad. Sci. U.S.A.98, 8342 (2001). (10.1073/pnas.111036998) / Proc. Natl. Acad. Sci. U.S.A. (2001)
H. Ohmori et al., Mol. Cell8, 7 (2001). (10.1016/S1097-2765(01)00278-7) / Mol. Cell (2001)
O. J. Becherel, R. P. Fuchs, Proc. Natl. Acad. Sci. U.S.A.98, 8566 (2001). (10.1073/pnas.141113398) / Proc. Natl. Acad. Sci. U.S.A. (2001)
Supported by CNRS and a grant from the Human Frontier Science Program (RG0351/1998-M). We thank V. Gasser for excellent technical support N. Koffel-Schwartz (UPR 9003) and B. Michel (Institut National de la Recherche Agronomique Jouy en Josas) for numerous insightful discussions and all members of UPR 9003 for comments.

Dates

Type	When
Created	22 years, 3 months ago (May 22, 2003, 4:33 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:14 p.m.)
Indexed	5 months, 1 week ago (March 19, 2025, 11:49 a.m.)
Issued	22 years, 3 months ago (May 23, 2003)
Published	22 years, 3 months ago (May 23, 2003)
Published Print	22 years, 3 months ago (May 23, 2003)

Funders 0

None

BibTeX

@article{Page_s_2003, title={Uncoupling of Leading- and Lagging-Strand DNA Replication During Lesion Bypass in Vivo}, volume={300}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1083964}, DOI={10.1126/science.1083964}, number={5623}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Pagès, Vincent and Fuchs, Robert P.}, year={2003}, month=may, pages={1300–1303} }

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