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Cell cycle-dependent strand bias for UV-induced mutations in the transcribed strand of excision repair-proficient human fibroblasts but not in repair-deficient cells

Journal Article · · Molecular and Cellular Biology; (United States)
; ; ; ;  [1]
  1. Michigan State University, East Lansing (United States)

To study the effect of nucleotide excision repair on the spectrum of mutations induced in diploid human fibroblasts by UV light (wavelength, 254 nm), the authors synchronized repair-proficient cells and irradiated them when the HPRT gene was about to be replicated (early S phase) so that there would be no time for repair in that gene before replication, or in G, phase 6 h prior to S, and determined the kinds and location of mutations in that gene. As a control, they also compared the spectra of mutations induced in synchronized populations of xeroderma pigmentosum cells (XP12BE cells, which are unable to excise UV-induced DNA damage). Among the 84 mutants sequenced, base substitutions predominated. Of the XP mutants from S or G[sub 1] and the repair-proficient mutants from S, [approximately]62% were G [center dot] C[r arrow]A [center dot] T. In the repair-proficient mutants from G[sub 1], 47% were. In mutants from the repair-proficient cells irradiated in S, 71% (10 of 14) of the premutagenic lesions were located in the transcribed strand; with mutants from such cells irradiated in G[sub 1], only 20% (3 of 15) were. The switch in strand bias supports preferential nucleotide excision repair of UV-induced damage in the transcribed strand of the HPRT gene.

OSTI ID:
7013715
Journal Information:
Molecular and Cellular Biology; (United States), Journal Name: Molecular and Cellular Biology; (United States) Vol. 11:4; ISSN 0270-7306; ISSN MCEBD4
Country of Publication:
United States
Language:
English

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