AI Article Synopsis
- The study examines how the XPC protein, crucial for repairing DNA damage, finds and interacts with damaged areas in mammalian cell nuclei, using experiments with GFP-tagged XPC to track its movements.
- Results show that XPC is usually moving in and out of the nucleus but slows down significantly when DNA damage occurs, especially after UV damage, suggesting its responsiveness to stress.
- A key finding is that XPC's presence in the nucleus is regulated by a shuttling mechanism, which increases its concentration in response to damage while preventing excessive probing of DNA.
Article Abstract
To investigate how the nucleotide excision repair initiator XPC locates DNA damage in mammalian cell nuclei we analyzed the dynamics of GFP-tagged XPC. Photobleaching experiments showed that XPC constantly associates with and dissociates from chromatin in the absence of DNA damage. DNA-damaging agents retard the mobility of XPC, and UV damage has the most pronounced effect on the mobility of XPC-GFP. XPC exhibited a surprising distinct dynamic behavior and subnuclear distribution compared with other NER factors. Moreover, we uncovered a novel regulatory mechanism for XPC. Under unchallenged conditions, XPC is continuously exported from and imported into the nucleus, which is impeded when NER lesions are present. XPC is omnipresent in the nucleus, allowing a quick response to genotoxic stress. To avoid excessive DNA probing by the low specificity of the protein, the steady-state level in the nucleus is controlled by nucleus-cytoplasm shuttling, allowing temporally higher concentrations of XPC in the nucleus under genotoxic stress conditions.
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| http://dx.doi.org/10.1242/jcs.031708 | DOI Listing |
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