8TLT

Cryo-EM structure of Rev1(deltaN)-Polzeta-DNA-dCTP complex

Summary for 8TLT

• Entry DOI: 10.2210/pdb8tlt/pdb
• EMDB information: 41372
• Descriptor: DNA polymerase zeta catalytic subunit, 2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE, DNA polymerase zeta processivity subunit, ... (11 entities in total)
• Functional Keywords: dna repair, dna replication, translesion dna synthesis, dna polymerase, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 8
• Total formula weight: 453463.98

Authors

Malik, R.,Aggarwal, A.K. (deposition date: 2023-07-27, release date: 2024-05-15, Last modification date: 2024-10-02)

Primary citation

Malik, R.,Johnson, R.E.,Ubarretxena-Belandia, I.,Prakash, L.,Prakash, S.,Aggarwal, A.K.
Cryo-EM structure of the Rev1-Pol zeta holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis.
Nat.Struct.Mol.Biol., 31:1394-1403, 2024

PubMed Abstract: Rev1-Polζ-dependent translesion synthesis (TLS) of DNA is crucial for maintaining genome integrity. To elucidate the mechanism by which the two polymerases cooperate in TLS, we determined the cryogenic electron microscopic structure of the Saccharomyces cerevisiae Rev1-Polζ holocomplex in the act of DNA synthesis (3.53 Å). We discovered that a composite N-helix-BRCT module in Rev1 is the keystone of Rev1-Polζ cooperativity, interacting directly with the DNA template-primer and with the Rev3 catalytic subunit of Polζ. The module is positioned akin to the polymerase-associated domain in Y-family TLS polymerases and is set ideally to interact with PCNA. We delineate the full extent of interactions that the carboxy-terminal domain of Rev1 makes with Polζ and identify potential new druggable sites to suppress chemoresistance from first-line chemotherapeutics. Collectively, our results provide fundamental new insights into the mechanism of cooperativity between Rev1 and Polζ in TLS.

PubMed: 38720088
DOI: 10.1038/s41594-024-01302-w

Experimental method

ELECTRON MICROSCOPY (2.85 Å)