Rearrangement of nucleosome structure during excision repair in xeroderma pigmentosum (group A) human fibroblasts

Rearrangements of chromatic structure during excision repair were examined in xeroderma pigmentosum (XP; complementation group A) human fibroblasts treated with the small-molecule alkylating agent methyl methanesulfonate (MMS). We observed normal levels of repair synthesis in these cells during the first 12 h after exposure to MMS, in contrast to the near zero incorporation of repair patches following exposure to u.v. light. Our results indicate that the relative nuclease sensitivity of newly repaired regions in MMS-treated XP (group A) cells is quantitatively similar to that of newly repaired regions in MMS-treated normal human fibroblasts. This enhanced sensitivity is accompanied by a marked under-representation of repair-incorporated nucleotides in isolated nucleosome core DNA. Pulse-chase experiments demonstrated that these regions rapidly undergo rearrangements in chromatin structure, and both the rate and extent of these rearrangements are similar to those observed in normal cells. (author)