Xeroderma pigmentosum type G (XPG) is a human genetic disease exhibiting extreme sensitivity to sunlight. XPG patients are defective XPG endonuclease, which is an enzyme essential for DNA repair of the major kinds of solar ultraviolet (UV)-induced DNA damages. Here we describe a novel dynamics of this protein within the cell nucleus after UV irradiation of human cells. Using confocal microscopy, we have localized the immunofluorescent, antigenic signal of XPG protein to foci throughout the cell nucleus. Our biochemical studies also established that XPG protein forms a tight association with nuclear structure(s). In human skin fibroblast cells, the number of XPG foci decreased within 2 h after UV irradiation, whereas total nuclear XPG fluorescence intensity remained constant, suggesting redistribution of XPG from a limited number of nuclear foci to the nucleus overall. Within 8 h after UV, most XPG antigenic signal was found as foci. Using j8-galactosidase-XPG fusion constructs (,B-gal-XPG) In recent decades, there has been substantial progress in understanding the basic structure of the cell nucleus and its implications in functional compartmentation (12). A proteinaceous framework known as the nuclear matrix or scaffold has been implicated in a variety of nuclear processes including DNA replication (13), excision repair (14, 15), and RNA transcription and processing (16-18). There is good evidence that regulatory proteins are situated near to the attachment sites of DNA loops to the nuclear matrix (19,20). This type of geometrical organization is thought to facilitate nuclear processes by efficiently reducing the search volume of transcriptional regulators for their cognate DNA elements (19). This principle may also apply to transcription-coupled NER by a mechanism that pre-positions DNA repair enzymes in transcriptionally active chromatin regions via association with nuclear matrix.The
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