Human DNA polymerase ? grasps the primer terminus to mediate DNA repair [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 576.8 Evolution
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015
• Mô tả vật lý: Size: p. 304-311 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261208
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Cancer; 4. Double-strand dna breaks; 5. Translesion synthesis; 6. X-ray crystallography

Tóm tắt

DNA polymerase ? protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase ? is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break?inducing agents, including ionizing radiation. Reported in this paper are crystal structures of the C-terminal polymerase domain from human polymerase ?, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase ? uses a specialized thumb subdomain to establish unique upstream contacts to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. Finally, these observations demonstrate how polymerase ? grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining.