This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Petermann, E.
Right arrow Articles by Caldecott, K. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petermann, E.
Right arrow Articles by Caldecott, K. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2006, p. 3319-3326, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3319-3326.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Chk1 Requirement for High Global Rates of Replication Fork Progression during Normal Vertebrate S Phase

Eva Petermann,1{dagger},{dagger} Apolinar Maya-Mendoza,2,{dagger} George Zachos,3,4 David A. F. Gillespie,3,4 Dean A. Jackson,2 and Keith W. Caldecott1*

Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom,1 The University of Manchester, Faculty of Life Sciences, The Mill, Sackville St., Manchester M60 1QD, United Kingdom,2 Beatson Institute for Cancer Research, Cancer Research UK, Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow G61 1BD, United Kingdom,3 Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom4

Received 4 November 2005/ Returned for modification 14 December 2005/ Accepted 2 February 2006

Chk1 protein kinase maintains replication fork stability in metazoan cells in response to DNA damage and DNA replication inhibitors. Here, we have employed DNA fiber labeling to quantify, for the first time, the extent to which Chk1 maintains global replication fork rates during normal vertebrate S phase. We report that replication fork rates in Chk1–/– chicken DT40 cells are on average half of those observed with wild-type cells. Similar results were observed if Chk1 was inhibited or depleted in wild-type DT40 cells or HeLa cells by incubation with Chk1 inhibitor or small interfering RNA. In addition, reduced rates of fork extension were observed with permeabilized Chk1–/– cells in vitro. The requirement for Chk1 for high fork rates during normal S phase was not to suppress promiscuous homologous recombination at replication forks, because inhibition of Chk1 similarly slowed fork progression in XRCC3–/– DT40 cells. Rather, we observed an increased number of replication fibers in Chk1–/– cells in which the nascent strand is single-stranded, supporting the idea that slow global fork rates in unperturbed Chk1–/– cells are associated with the accumulation of aberrant replication fork structures.

* Corresponding author. Mailing address: Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, United Kingdom. Phone for Keith W. Caldecott: 44-0-1273-877519. Fax: 44-0-1273-678121. E-mail: k.w.caldecott{at}sussex.ac.uk. Phone for Eva Petermann: 44-0-1273-877511. Fax: 44-0-1273-678121. E-mail: e.k.peterman{at}sussex.ac.uk.

{dagger} These two authors contributed equally.

Molecular and Cellular Biology, April 2006, p. 3319-3326, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3319-3326.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Krude, T., Christov, C. P., Hyrien, O., Marheineke, K. (2009). Y RNA functions at the initiation step of mammalian chromosomal DNA replication. J. Cell Sci. 122: 2836-2845 [Abstract] [Full Text]  
  • Wilsker, D., Petermann, E., Helleday, T., Bunz, F. (2008). Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control. Proc. Natl. Acad. Sci. USA 105: 20752-20757 [Abstract] [Full Text]  
  • McCall, C. M., Miliani de Marval, P. L., Chastain, P. D. II, Jackson, S. C., He, Y. J., Kotake, Y., Cook, J. G., Xiong, Y. (2008). Human Immunodeficiency Virus Type 1 Vpr-Binding Protein VprBP, a WD40 Protein Associated with the DDB1-CUL4 E3 Ubiquitin Ligase, Is Essential for DNA Replication and Embryonic Development. Mol. Cell. Biol. 28: 5621-5633 [Abstract] [Full Text]  
  • Zabludoff, S. D., Deng, C., Grondine, M. R., Sheehy, A. M., Ashwell, S., Caleb, B. L., Green, S., Haye, H. R., Horn, C. L., Janetka, J. W., Liu, D., Mouchet, E., Ready, S., Rosenthal, J. L., Queva, C., Schwartz, G. K., Taylor, K. J., Tse, A. N., Walker, G. E., White, A. M. (2008). AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Molecular Cancer Therapeutics 7: 2955-2966 [Abstract] [Full Text]  
  • Scorah, J., Dong, M.-Q., Yates, J. R. III, Scott, M., Gillespie, D., McGowan, C. H. (2008). A Conserved Proliferating Cell Nuclear Antigen-interacting Protein Sequence in Chk1 Is Required for Checkpoint Function. J. Biol. Chem. 283: 17250-17259 [Abstract] [Full Text]  
  • Petermann, E., Helleday, T., Caldecott, K. W. (2008). Claspin Promotes Normal Replication Fork Rates in Human Cells. Mol. Biol. Cell 19: 2373-2378 [Abstract] [Full Text]  
  • Yang, X. H., Shiotani, B., Classon, M., Zou, L. (2008). Chk1 and Claspin potentiate PCNA ubiquitination. Genes Dev. 22: 1147-1152 [Abstract] [Full Text]  
  • Unsal-Kacmaz, K., Chastain, P. D., Qu, P.-P., Minoo, P., Cordeiro-Stone, M., Sancar, A., Kaufmann, W. K. (2007). The Human Tim/Tipin Complex Coordinates an Intra-S Checkpoint Response to UV That Slows Replication Fork Displacement. Mol. Cell. Biol. 27: 3131-3142 [Abstract] [Full Text]  
  • Crest, J., Oxnard, N., Ji, J.-Y., Schubiger, G. (2007). Onset of the DNA Replication Checkpoint in the Early Drosophila Embryo. Genetics 175: 567-584 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»