8U0O

Synaptic complex of human DNA polymerase Lambda DL variant engaged on a DNA double-strand break containing an unpaired 3' primer terminus

8U0O の概要

• エントリーDOI: 10.2210/pdb8u0o/pdb
• 分子名称: DNA polymerase lambda, DNA (5'-D(*AP*CP*GP*CP*GP*GP*CP*A)-3'), DNA (5'-D(P*GP*CP*CP*GP*CP*GP*TP*A)-3'), ... (8 entities in total)
• 機能のキーワード: nonhomologous end-joining, base excision repair, dna polymerase, transferase, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 43080.20

構造登録者

Kaminski, A.M.,Pedersen, L.C.,Bebenek, K.,Kunkel, T.A.,Chiruvella, K.K.,Ramsden, D.A. (登録日: 2023-08-29, 公開日: 2024-03-13)

主引用文献

Kaminski, A.M.,Chiruvella, K.K.,Ramsden, D.A.,Bebenek, K.,Kunkel, T.A.,Pedersen, L.C.
DNA polymerase lambda Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining.
DNA Repair (Amst), 136:103645-103645, 2024

PubMed Abstract: DNA polymerases lambda (Polλ) and mu (Polμ) are X-Family polymerases that participate in DNA double-strand break (DSB) repair by the nonhomologous end-joining pathway (NHEJ). Both polymerases direct synthesis from one DSB end, using template derived from a second DSB end. In this way, they promote the NHEJ ligation step and minimize the sequence loss normally associated with this pathway. The two polymerases differ in cognate substrate, as Polλ is preferred when synthesis must be primed from a base-paired DSB end, while Polμ is required when synthesis must be primed from an unpaired DSB end. We generated a Polλ variant (Polλ) that retained canonical Polλ activity on a paired end-albeit with reduced incorporation fidelity. We recently discovered that the variant had unexpectedly acquired the activity previously unique to Polμ-synthesis from an unpaired primer terminus. Though the sidechains of the Loop1 region make no contact with the DNA substrate, Polλ Loop1 amino acid sequence is surprisingly essential for its unique activity during NHEJ. Taken together, these results underscore that the Loop1 region plays distinct roles in different Family X polymerases.

PubMed: 38428373
DOI: 10.1016/j.dnarep.2024.103645

実験手法

X-RAY DIFFRACTION (2.05 Å)