Xeroderma pigmentosum group A protein loads as a separate factor onto DNA lesions

Nucleotide excision repair (NER) is the main DNA repair pathway in mammals for removal of UV-induced lesions. NER involves the concerted action of more than 25 polypeptides in a coordinated fashion. The xeroderma pigmentosum group A protein (XPA) has been suggested to function as a central organizer and damage verifier in NER. How XPA reaches DNA lesions and how the protein is distributed in time and space in living cells are unknown. Here we studied XPA in vivo by using a cell line stably expressing physiological levels of functional XPA fused to green fluorescent protein and by applying quantitative fluorescence microscopy. The majority of XPA moves rapidly through the nucleoplasm with a diffusion rate different from those of other NER factors tested, arguing against a preassembled XPA-containing NER complex. DNA damage induced a transient ( approximately 5-min) immobilization of maximally 30% of XPA. Immobilization depends on XPC, indicating that XPA is not the initial lesion recognition protein in vivo. Moreover, loading of replication protein A on NER lesions was not dependent on XPA. Thus, XPA participates in NER by incorporation of free diffusing molecules in XPC-dependent NER-DNA complexes. This study supports a model for a rapid consecutive assembly of free NER factors, and a relatively slow simultaneous disassembly, after repair

Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

Highlights of the 2009 scientific sessions of the European Society of Cardiology

The annual congress of the European Society of Cardiology (ESC) was held in Barcelona, Spain, August 29 to September 2, 2009. The total attendance was 31,323 participants from 136 different countries. Excellent congress facilities hosted 237 pre-arranged sessions in 30 meeting rooms running in parallel, including several joint sessions in collaboration with other societies (e.g., the American College of Cardiology, the American Heart Association, and the World Heart Federation). A total of 9,848 abstracts from 96 different countries was submitted, and 4,085 (42%) abstracts were selected for presentation

Transanal Endoscopic Microsurgery with or without Completion Total Mesorectal Excision for T2 and T3 Rectal Carcinoma

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