Crossref journal-article
Rockefeller University Press
The Journal of Cell Biology (291)
Abstract

Alkylating agents, such as methyl methanesulfonate (MMS), damage DNA and activate the DNA damage checkpoint. Although many of the checkpoint proteins that transduce damage signals have been identified and characterized, the mechanism that senses the damage and activates the checkpoint is not yet understood. To address this issue for alkylation damage, we have reconstituted the checkpoint response to MMS in Xenopus egg extracts. Using four different indicators for checkpoint activation (delay on entrance into mitosis, slowing of DNA replication, phosphorylation of the Chk1 protein, and physical association of the Rad17 checkpoint protein with damaged DNA), we report that MMS-induced checkpoint activation is dependent upon entrance into S phase. Additionally, we show that the replication of damaged double-stranded DNA, and not replication of damaged single-stranded DNA, is the molecular event that activates the checkpoint. Therefore, these data provide direct evidence that replication forks are an obligate intermediate in the activation of the DNA damage checkpoint.

Bibliography

Stokes, M. P., Van Hatten, R., Lindsay, H. D., & Michael, W. M. (2002). DNA replication is required for the checkpoint response to damaged DNA in Xenopus egg extracts. The Journal of Cell Biology, 158(5), 863–872.

Authors 4
  1. Matthew P. Stokes (first)
  2. Ruth Van Hatten (additional)
  3. Howard D. Lindsay (additional)
  4. W. Matthew Michael (additional)
References 44 Referenced 61
  1. 10.1101/gad.914401 / Genes Dev. (2001)
  2. 10.1038/35082110 / Nature. (2001)
  3. 10.1074/jbc.M001244200 / J. Biol. Chem. (2000)
  4. 10.1038/35003501 / Nature. (2000)
  5. {'key': '2023072213443839200_BIB5'}
  6. 10.1016/S0960-9822(99)00263-8 / Curr. Biol. (2000)
  7. 10.1002/j.1460-2075.1995.tb00269.x / EMBO J. (1995)
  8. 10.1091/mbc.11.5.1535 / Mol. Biol. Cell. (2000)
  9. 10.1101/gad.842500 / Genes Dev. (2000)
  10. 10.1093/embo-reports/kvd076 / EMBO Rep. (2000)
  11. 10.1128/MCB.21.10.3289-3301.2001 / Mol. Cell. Biol. (2001)
  12. 10.1126/science.1063827 / Science. (2001)
  13. 10.1083/jcb.142.6.1559 / J. Cell Biol. (1998)
  14. 10.1016/S0092-8674(00)81482-8 / Cell. (1998)
  15. 10.1073/pnas.201373498 / Proc. Natl. Acad. Sci. USA. (2001)
  16. 10.1016/S0092-8674(00)81209-X / Cell. (1998)
  17. 10.1016/S0955-0674(02)00312-5 / Curr. Opin. Cell Biol. (2002)
  18. 10.1101/gad.903501 / Genes Dev. (2001)
  19. 10.1126/science.282.5395.1886 / Science. (1998)
  20. 10.1126/science.289.5487.2133 / Science. (2000)
  21. 10.1016/S0968-0004(00)01560-7 / Trends Biochem. Sci. (2000)
  22. 10.1016/S0091-679X(08)60298-8 / Methods Cell Biol. (1991)
  23. 10.1093/emboj/18.16.4485 / EMBO J. (1999)
  24. 10.1016/S0962-8924(00)01773-6 / Trends Cell Biol. (2000)
  25. 10.1016/S0027-5107(77)80031-6 / Mutat. Res. (1977)
  26. 10.1016/0092-8674(95)90481-6 / Cell. (1995)
  27. 10.1093/genetics/145.1.45 / Genetics. (1997)
  28. 10.1093/emboj/18.22.6561 / EMBO J. (1999)
  29. 10.1073/pnas.231364598 / Proc. Natl. Acad. Sci. USA. (2001)
  30. {'key': '2023072213443839200_BIB30', 'first-page': '4375', 'volume': '59', 'year': '1999', 'journal-title': 'Cancer Res.'} / Cancer Res. (1999)
  31. 10.1091/mbc.10.12.3991 / Mol. Biol. Cell. (1999)
  32. 10.1128/MCB.18.9.5485 / Mol. Cell. Biol. (1998)
  33. 10.1038/27007 / Nature. (1998)
  34. 10.1073/pnas.90.17.7985 / Proc. Natl. Acad. Sci. USA. (1993)
  35. 10.1038/35055000 / Nat. Cell Biol. (2001)
  36. 10.1038/35087607 / Nature. (2001)
  37. 10.1016/0092-8674(94)90573-8 / Cell. (1994)
  38. 10.1093/emboj/17.19.5679 / EMBO J. (1998)
  39. 10.1016/S1097-2765(00)80052-0 / Mol. Cell. (1998)
  40. {'key': '2023072213443839200_BIB40'}
  41. 10.1126/science.3291120 / Science. (1988)
  42. 10.1126/science.290.5500.2309 / Science. (2000)
  43. 10.1038/35044005 / Nature. (2000)
  44. 10.1101/gad.950302 / Genes Dev. (2002)
Dates
Type When
Created 22 years, 11 months ago (Sept. 3, 2002, 3:13 p.m.)
Deposited 2 years, 1 month ago (July 22, 2023, 9:45 a.m.)
Indexed 1 year ago (Aug. 4, 2024, 3:52 p.m.)
Issued 23 years ago (Sept. 2, 2002)
Published 23 years ago (Sept. 2, 2002)
Published Online 22 years, 11 months ago (Sept. 3, 2002)
Published Print 23 years ago (Sept. 2, 2002)
Funders 0

None

@article{Stokes_2002, title={DNA replication is required for the checkpoint response to damaged DNA in Xenopus egg extracts}, volume={158}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200204127}, DOI={10.1083/jcb.200204127}, number={5}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Stokes, Matthew P. and Van Hatten, Ruth and Lindsay, Howard D. and Michael, W. Matthew}, year={2002}, month=sep, pages={863–872} }