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The architecture of yeast DNA polymerase ?.

ABSTRACT: DNA polymerase ? (Pol?) is specialized for the extension step of translesion DNA synthesis (TLS). Despite its central role in maintaining genome integrity, little is known about its overall architecture. Initially identified as a heterodimer of the catalytic subunit Rev3 and the accessory subunit Rev7, yeast Pol? has recently been shown to form a stable four-subunit enzyme (Pol?-d) upon the incorporation of Pol31 and Pol32, the accessory subunits of yeast Pol?. To understand the 3D architecture and assembly of Pol? and Pol?-d, we employed electron microscopy. We show here how the catalytic and accessory subunits of Pol? and Pol?-d are organized relative to each other. In particular, we show that Pol?-d has a bilobal architecture resembling the replicative polymerases and that Pol32 lies in proximity to Rev7. Collectively, our study provides views of Pol? and Pol?-d and a structural framework for understanding their roles in DNA damage bypass.

SUBMITTER: Gomez-Llorente Y

PROVIDER: S-EPMC3883112 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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The architecture of yeast DNA polymerase ζ.

Gómez-Llorente Yacob Y Malik Radhika R Jain Rinku R Choudhury Jayati Roy JR Johnson Robert E RE Prakash Louise L Prakash Satya S Ubarretxena-Belandia Iban I Aggarwal Aneel K AK

Cell reports 20131010 1

DNA polymerase ζ (Polζ) is specialized for the extension step of translesion DNA synthesis (TLS). Despite its central role in maintaining genome integrity, little is known about its overall architecture. Initially identified as a heterodimer of the catalytic subunit Rev3 and the accessory subunit Rev7, yeast Polζ has recently been shown to form a stable four-subunit enzyme (Polζ-d) upon the incorporation of Pol31 and Pol32, the accessory subunits of yeast Polδ. To understand the 3D architecture ...[more]

PMID: 24120860

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Mutator alleles of yeast DNA polymerase zeta.

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| S-EPMC2128049 | biostudies-literature

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Pol31 and Pol32 subunits of yeast DNA polymerase δ are also essential subunits of DNA polymerase ζ.

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Yeast DNA polymerase ζ maintains consistent activity and mutagenicity across a wide range of physiological dNTP concentrations.

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Loss of DNA polymerase zeta enhances spontaneous tumorigenesis.

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A novel role of DNA polymerase λ in translesion synthesis in conjunction with DNA polymerase ζ.

Project description:By extending synthesis opposite from a diverse array of DNA lesions, DNA polymerase (Pol) ζ performs a crucial role in translesion synthesis (TLS). In yeast and cancer cells, Rev1 functions as an indispensable scaffolding component of Polζ and it imposes highly error-prone TLS upon Polζ. However, for TLS that occurs during replication in normal human cells, Rev1 functions instead as a scaffolding component of Pols η, ι, and κ and Rev1-dependent TLS by these Pols operates in a predominantly error-free manner. The lack of Rev1 requirement for Polζ function in TLS in normal cells suggested that some other protein substitutes for this Rev1 role. Here, we identify a novel role of Polλ as an indispensable scaffolding component of Polζ. TLS studies opposite a number of DNA lesions support the conclusion that as an integral component, Polλ adapts Polζ-dependent TLS to operate in a predominantly error-free manner in human cells, essential for genome integrity and cellular homeostasis.

| S-EPMC7898466 | biostudies-literature

Bypass of DNA interstrand crosslinks by a Rev1-DNA polymerase ζ complex.

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