5N8A

Structure of RPA70N in complex with PrimPol (fragment 480-560)

5N8A の概要

• エントリーDOI: 10.2210/pdb5n8a/pdb
• 関連するPDBエントリー: 5N85
• 分子名称: DNA-directed primase/polymerase protein, Replication protein A 70 kDa DNA-binding subunit (3 entities in total)
• 機能のキーワード: complex, replication, basic cleft, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: Q96LW4 P27694
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24515.37

構造登録者

Brissett, N.C.,Doherty, A.J. (登録日: 2017-02-23, 公開日: 2017-06-07, 最終更新日: 2024-01-17)

主引用文献

Guilliam, T.A.,Brissett, N.C.,Ehlinger, A.,Keen, B.A.,Kolesar, P.,Taylor, E.M.,Bailey, L.J.,Lindsay, H.D.,Chazin, W.J.,Doherty, A.J.
Molecular basis for PrimPol recruitment to replication forks by RPA.
Nat Commun, 8:15222-15222, 2017

PubMed Abstract: DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA. Using biophysical and crystallographic approaches, we identify that PrimPol possesses two RPA-binding motifs and ascertained the key residues required for these interactions. We demonstrate that one of these motifs is critical for PrimPol's recruitment to stalled replication forks in vivo. In addition, biochemical analysis reveals that RPA serves to stimulate the primase activity of PrimPol. Together, these findings provide significant molecular insights into PrimPol's mode of recruitment to stalled forks to facilitate repriming and restart.

PubMed: 28534480
DOI: 10.1038/ncomms15222

実験手法

X-RAY DIFFRACTION (1.28 Å)