Nucleic Acids Research, Vol 27, Issue 16 3276-3282, Copyright © 1999 by Oxford University Press
PP Van Sloun, JG Jansen, G Weeda, LH Mullenders, AA van Zeeland, PH Lohman and H Vrieling
In this study the role of nucleotide excision repair (NER) in protecting
mouse embryonic stem (ES) cells against the genotoxic effects of
UV-photolesions was analysed. Repair of cyclobutane pyrimidine dimers (CPD)
in transcribed genes could not be detected whereas the removal of (6-4)
photoproducts (6-4PP) was incomplete, already reaching its maximum (30%) 4
h after irradiation. Measurements of repair replication revealed a
saturation of NER activity at UV doses >5 J/m2 while at a lower dose
(2.5 J/m2) the repair kinetics were similar to those in murine embryonic
fibroblasts (MEFs). Cytotoxic and mutagenic effects of photolesions were
determined in ES cells differing in NER activity. ERCC1-deficient ES cells
were hypermutable (10-fold) compared to wild-type cells, indicating that at
physiologically relevant doses ES cells efficiently remove photolesions.
The effect of the NER deficiency on cytoxicity was only 2-fold. Exposure to
high UV doses (10 J/m2) resulted in a rapid and massive induction of
apoptosis. Possibly, to avoid the accumulation of mutated cells, ES cells
rely on the induction of a strong apoptotic response with a simultaneous
shutting down of NER activity.
ARTICLES
The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage
Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, PO Box 9503, 2300 RA Leiden, The Netherlands.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Maynard, A. M. Swistowska, J. W. Lee, Y. Liu, S.-T. Liu, A. B. Da Cruz, M. Rao, N. C. de Souza-Pinto, X. Zeng, and V. A. Bohr Human Embryonic Stem Cells Have Enhanced Repair of Multiple Forms of DNA Damage Stem Cells, September 1, 2008; 26(9): 2266 - 2274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Mueller, J. Luetzkendorf, T. Mueller, K. Reichelt, H. Simon, and H.-J. Schmoll Presence of Mesenchymal Stem Cells in Human Bone Marrow After Exposure to Chemotherapy: Evidence of Resistance to Apoptosis Induction Stem Cells, December 1, 2006; 24(12): 2753 - 2765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. U. Bracker, B. Giebel, J. Spanholtz, U. R. Sorg, L. Klein-Hitpass, T. Moritz, and J. Thomale Stringent Regulation of DNA Repair During Human Hematopoietic Differentiation: A Gene Expression and Functional Analysis Stem Cells, March 1, 2006; 24(3): 722 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Jansen, A. Tsaalbi-Shtylik, P. Langerak, F. Calléja, C. M. Meijers, H. Jacobs, and N. de Wind The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis Nucleic Acids Res., January 13, 2005; 33(1): 356 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Saretzki, L. Armstrong, A. Leake, M. Lako, and T. von Zglinicki Stress Defense in Murine Embryonic Stem Cells Is Superior to That of Various Differentiated Murine Cells Stem Cells, November 1, 2004; 22(6): 962 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hong and P. J. Stambrook Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation PNAS, October 5, 2004; 101(40): 14443 - 14448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Cervantes, J. R. Stringer, C. Shao, J. A. Tischfield, and P. J. Stambrook Embryonic stem cells and somatic cells differ in mutation frequency and type PNAS, March 19, 2002; 99(6): 3586 - 3590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jansen, A. K. Olsen, R. Wiger, H. Naegeli, P. de Boer, F. van der Hoeven, J. A. Holme, G. Brunborg, and L. Mullenders Nucleotide excision repair in rat male germ cells: low level of repair in intact cells contrasts with high dual incision activity in vitro Nucleic Acids Res., April 15, 2001; 29(8): 1791 - 1800. [Abstract] [Full Text] [PDF]
|
|