The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage | Zendy

Petra P. H. Van Sloun | Zendy; Jacob G. Jansen | Zendy; Geert Weeda | Zendy; Leon H.F. Mullenders | Zendy; A.A. van Zeeland | Zendy; P.H.M. Lohman | Zendy; Harry Vrieling | Zendy

Open Access

The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage

Author(s) -

Petra P. H. Van Sloun,

Jacob G. Jansen,

Geert Weeda,

Leon H.F. Mullenders,

A.A. van Zeeland,

P.H.M. Lohman,

Harry Vrieling

Publication year - 1999

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/27.16.3276

Subject(s) - pyrimidine dimer , nucleotide excision repair , biology , embryonic stem cell , dna damage , dna repair , microbiology and biotechnology , ercc1 , apoptosis , dna , genetics , gene

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.

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