Summary information and primary citation
- PDB-id
-
8tlq;
SNAP-derived features in text and
JSON formats
- Class
- DNA binding protein-DNA
- Method
- cryo-EM (3.53 Å)
- Summary
- cryo-EM structure of the rev1-polzeta-DNA-dctp
complex
- Reference
-
Malik R, Johnson RE, Ubarretxena-Belandia I, Prakash L,
Prakash S, Aggarwal AK (2024): "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. doi: 10.1038/s41594-024-01302-w.
- 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.
