Atl1 Regulates Choice between Global Genome and Transcription-Coupled Repair of O⁶-Alkylguanines

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• 作者：Vitaly?F. Latypov ; Julie?L. Tubbs ; Am ; a?J. Watson ; Andrew?S. Marriott ; Gail McGown ; Mary Thorncroft ; Oliver?J. Wilkinson ; Pattama Senthong ; Amna Butt ; Andrew?S. Arvai ; Christopher?L. Millington ; Andrew?C. Povey ; David?M. Williams ; Mauro?F. Santibanez-Koref ; John?A. Tainer ; Geoffrey?P. Margison
• 刊名：Molecular Cell
• 出版年：2012
• 出版时间：13 July, 2012
• 年：2012
• 卷：47
• 期：1
• 页码：50-60
• 全文大小：3679 K

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Summary

Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that?in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O⁶-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O⁶-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O⁶-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by?NER.