Lack of DNA polymerase eta and the attendant defect in bypass replication of @entity7391 dimers induced in DNA by ultraviolet light (UV) underlie the enhanced mutagenesis and carcinogenesis observed in @entity2173 variant ( @entity44374 ). We investigated whether diploid @entity44374 fibroblasts growing in culture are also more susceptible to UV-induced clastogenesis than normal @entity1 fibroblasts (NHF). This study utilized diploid fibroblasts immortalized by the ectopic expression of @entity1 telomerase. The cell lines displayed checkpoint responses to DNA damage comparable with those measured in the parental strains. Shortly after exposure to low doses of UVC (< or =4 J/m2), @entity44374 cells accumulated daughter strand gaps in excess of normal controls (>25-fold). Daughter strand gaps generated in UV-irradiated S phase cells are potential precursors of chromatid-type chromosomal aberrations. Nonetheless, chromatid-type chromosomal aberrations were only 1.5 to 2 times more abundant in @entity44374 than in NHF exposed to the same UVC dose. @entity44374 cells, however, displayed S phase delays at lower doses of UVC and for longer periods of time than NHF. These results support the hypothesis that aberrant DNA structures activate S phase checkpoint responses that increase the time available for postreplication repair. Alternatively, cells that cannot be properly repaired remain permanently arrested and never reach mitosis. These responses protect @entity1 cells from chromosomal aberrations, especially when other pathways, such as accurate lesion bypass, are lost.

DNA damage responses protect XXXX variant from UVC-induced clastogenesis.

@entity1 :: ('9606', 'Species') :: ['human'] @entity2173 :: ('MESH:D014983', 'Disease') :: ['xeroderma pigmentosum'] @entity7391 :: ('MESH:C030986', 'Chemical') :: ['pyrimidine'] @entity44374 :: ('5429', 'Gene') :: ['XP-V']
@entity2173 :: (MESH:D014983,Disease) :: ['xeroderma pigmentosum']
