7M0B

Pre-catalytic quaternary complex of DNA Polymerase Lambda with bound mismatched DSB and incoming dUMPNPP

7M0B の概要

• エントリーDOI: 10.2210/pdb7m0b/pdb
• 分子名称: DNA polymerase lambda, SULFATE ION, 1,2-ETHANEDIOL, ... (12 entities in total)
• 機能のキーワード: nonhomologous end-joining, base excision repair, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 45839.00

構造登録者

Kaminski, A.M.,Bebenek, K.,Pedersen, L.C.,Kunkel, T.A. (登録日: 2021-03-10, 公開日: 2022-03-16, 最終更新日: 2023-10-25)

主引用文献

Kaminski, A.M.,Chiruvella, K.K.,Ramsden, D.A.,Bebenek, K.,Kunkel, T.A.,Pedersen, L.C.
Analysis of diverse double-strand break synapsis with Pol lambda reveals basis for unique substrate specificity in nonhomologous end-joining.
Nat Commun, 13:3806-3806, 2022

PubMed Abstract: DNA double-strand breaks (DSBs) threaten genomic stability, since their persistence can lead to loss of critical genetic information, chromosomal translocations or rearrangements, and cell death. DSBs can be repaired through the nonhomologous end-joining pathway (NHEJ), which processes and ligates DNA ends efficiently to prevent or minimize sequence loss. Polymerase λ (Polλ), one of the Family X polymerases, fills sequence gaps of DSB substrates with a strict specificity for a base-paired primer terminus. There is little information regarding Polλ's approach to engaging such substrates. We used in vitro polymerization and cell-based NHEJ assays to explore the contributions of conserved loop regions toward DSB substrate specificity and utilization. In addition, we present multiple crystal structures of Polλ in synapsis with varying biologically relevant DSB end configurations, revealing how key structural features and hydrogen bonding networks work in concert to stabilize these tenuous, potentially cytotoxic DNA lesions during NHEJ.

PubMed: 35778389
DOI: 10.1038/s41467-022-31278-4

実験手法

X-RAY DIFFRACTION (2 Å)