Nucleotide excision repair phenotype of human acute myeloid leukemia cell lines at various stages of differentiation.
In previous studies it was shown that nucleotide excision repair (NER) is strongly attenuated at the global genome level in terminally differentiated neuron-like cells. NER was measured in several human acute myeloid leukemia cell lines, before and after differentiation into macrophage-like cells. Repair of cisplatin intrastrand GTG crosslinks in differentiated cells was strongly attenuated. There were also some variations between repair levels in naïve cells, but these were not correlated with the degree of differentiation. By contrast, the proficient repair of UV-induced (6-4)pyrimidine-pyrimidone photoproducts [(6-4)PPs] was not affected by differentiation. Although cyclobutane pyrimidine dimers (CPDs) were poorly repaired at the global genome level in all cell lines, differentiated or not, they were very efficiently removed from the transcribed strand of an active gene, indicating that transcription-coupled repair (TCR) is proficient in each cell line. CPDs were also removed from the non-transcribed strand of an active gene better than at the overall global genome level. This relatively efficient repair of the non-transcribed strand of active genes, when compared with global genomic repair (GGR), has been described previously in neuron-like cells and termed differentiation-associated repair (DAR). Here we show that it also can occur in actively growing cells that display poor GGR.
Hsu
Pei-hsin
PH
Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.
Hanawalt
Philip C
PC
Nouspikel
Thierry
T
D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011740:Pyrimidine Dimers / Q000378:metabolism
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004273:DNA, Neoplasm; D011740:Pyrimidine Dimers; D002945:Cisplatin