Abstract
Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light–induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol) II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5′-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II.
References
30
Referenced
217
-
J. R. Mitchell, J. H. Hoeijmakers, L. J. Niedernhofer, Curr. Opin. Cell Biol.15, 232 (2003).
(
10.1016/S0955-0674(03)00018-8
) / Curr. Opin. Cell Biol. (2003) -
I. Mellon, G. Spivak, P. C. Hanawalt, Cell51, 241 (1987).
(
10.1016/0092-8674(87)90151-6
) / Cell (1987) -
S. Tornaletti, B. A. Donahue, D. Reines, P. C. Hanawalt, J. Biol. Chem.272, 31719 (1997).
(
10.1074/jbc.272.50.31719
) / J. Biol. Chem. (1997) -
J. S. Mei Kwei et al., Biochem. Biophys. Res. Commun.320, 1133 (2004).
(
10.1016/j.bbrc.2004.06.066
) / Biochem. Biophys. Res. Commun. (2004) -
T. T. Saxowsky, P. W. Doetsch, Chem. Rev.106, 474 (2006).
(
10.1021/cr040466q
) / Chem. Rev. (2006) -
C. P. Selby, R. Drapkin, D. Reinberg, A. Sancar, Nucleic Acids Res.25, 787 (1997).
(
10.1093/nar/25.4.787
) / Nucleic Acids Res. (1997) -
A. Tremeau-Bravard, T. Riedl, J. M. Egly, M. E. Dahmus, J. Biol. Chem.279, 7751 (2004).
(
10.1074/jbc.M309853200
) / J. Biol. Chem. (2004) -
D. Mu, A. Sancar, J. Biol. Chem.272, 7570 (1997).
(
10.1074/jbc.272.12.7570
) / J. Biol. Chem. (1997) -
A. Sancar, Annu. Rev. Biochem.65, 43 (1996).
(
10.1146/annurev.bi.65.070196.000355
) / Annu. Rev. Biochem. (1996) -
S. Prakash, L. Prakash, Mutat. Res.451, 13 (2000).
(
10.1016/S0027-5107(00)00037-3
) / Mutat. Res. (2000) 10.1016/j.molcel.2004.11.040
- Materials and methods are available as supporting material on Science Online.
10.1126/science.1059495
10.1016/j.cell.2004.10.016
-
M. L. Kireeva, N. Komissarova, D. S. Waugh, M. Kashlev, J. Biol. Chem.275, 6530 (2000).
(
10.1074/jbc.275.9.6530
) / J. Biol. Chem. (2000) -
H. Ling, F. Boudsocq, B. S. Plosky, R. Woodgate, W. Yang, Nature424, 1083 (2003).
(
10.1038/nature01919
) / Nature (2003) -
Y. Li et al., Nat. Struct. Mol. Biol.11, 784 (2004).
(
10.1038/nsmb792
) / Nat. Struct. Mol. Biol. (2004) -
B. A. Donahue, S. Yin, J. S. Taylor, D. Reines, P. C. Hanawalt, Proc. Natl. Acad. Sci. U.S.A.91, 8502 (1994).
(
10.1073/pnas.91.18.8502
) / Proc. Natl. Acad. Sci. U.S.A. (1994) -
R. A. Verhage, J. Heyn, P. van de Putte, J. Brouwer, Mol. Gen. Genet.254, 284 (1997).
(
10.1007/s004380050417
) / Mol. Gen. Genet. (1997) -
A. M. Deaconescu et al., Cell124, 507 (2006).
(
10.1016/j.cell.2005.11.045
) / Cell (2006) -
C. P. Selby, A. Sancar, J. Biol. Chem.272, 1885 (1997).
(
10.1074/jbc.272.3.1885
) / J. Biol. Chem. (1997) -
A. H. Sarker et al., Mol. Cell20, 187 (2005).
(
10.1016/j.molcel.2005.09.022
) / Mol. Cell (2005) -
J. Q. Svejstrup, J. Cell Sci.116, 447 (2003).
(
10.1242/jcs.00271
) / J. Cell Sci. (2003) -
M. Wind, D. Reines, Bioessays22, 327 (2000).
(
10.1002/(SICI)1521-1878(200004)22:4<327::AID-BIES3>3.0.CO;2-4
) / Bioessays (2000) -
S. K. Lee, S. L. Yu, L. Prakash, S. Prakash, Mol. Cell. Biol.22, 4383 (2002).
(
10.1128/MCB.22.12.4383-4389.2002
) / Mol. Cell. Biol. (2002) -
J. P. Laine, J. M. Egly, EMBO J.25, 387 (2006).
(
10.1038/sj.emboj.7600933
) / EMBO J. (2006) -
C. P. Selby, A. Sancar, Proc. Natl. Acad. Sci. U.S.A.94, 11205 (1997).
(
10.1073/pnas.94.21.11205
) / Proc. Natl. Acad. Sci. U.S.A. (1997) -
A. Aboussekhra et al., Cell80, 859 (1995).
(
10.1016/0092-8674(95)90289-9
) / Cell (1995) -
E. C. Woudstra et al., Nature415, 929 (2002).
(
10.1038/415929a
) / Nature (2002) - We thank H. Kettenberger K. Armache current members of the Cramer laboratory A. Muschielok J. Michaelis and C. Schulze-Briese for help. This work was supported by the Deutsche Forschungsgemeinschaft the Sonderforschungsbereich 646 the Volkswagen-Stiftung and the Fonds der chemischen Industrie. Part of this work was performed at the Swiss Light Source at the Paul Scherrer Institute Villigen Switzerland. Structure coordinates and reflection files are deposited in the Protein Data Bank under accession numbers 2ja5 2ja6 2ja7 and 2ja8 for complexes A B C and D respectively.
Dates
Type | When |
---|---|
Created | 18 years, 6 months ago (Feb. 8, 2007, 4:33 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 10, 2024, 4:40 a.m.) |
Indexed | 7 hours, 22 minutes ago (Aug. 27, 2025, 11:39 a.m.) |
Issued | 18 years, 6 months ago (Feb. 9, 2007) |
Published | 18 years, 6 months ago (Feb. 9, 2007) |
Published Print | 18 years, 6 months ago (Feb. 9, 2007) |
@article{Brueckner_2007, title={CPD Damage Recognition by Transcribing RNA Polymerase II}, volume={315}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1135400}, DOI={10.1126/science.1135400}, number={5813}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Brueckner, Florian and Hennecke, Ulrich and Carell, Thomas and Cramer, Patrick}, year={2007}, month=feb, pages={859–862} }