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Eukaryotic Y-Family Polymerases: A Biochemical and Structural Perspective

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Nucleic Acid Polymerases

Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 30))

Abstract

Classical DNA polymerases, which replicate DNA rapidly and with high fidelity, stall upon encountering DNA damage. Thus nonclassical polymerases, which have evolved to accommodate DNA damage, are necessary to overcome these replication blocks. These nonclassical polymerases mainly belong to the Y-family and replicate DNA slower and with lower fidelity than their classical counterparts. Y-family polymerases employ surprising strategies to incorporate nucleotides opposite DNA damage. These include the use of larger and less constrained active sites, the use of Hoogsteen base pairing, and the use of amino acid side chains as templates. Y-family polymerases also engage in protein–protein interactions that are important for their recruitment to stalled replication forks and the coordination of their activities on the DNA. These polymerases function within a dynamic network of protein–protein interactions that are mediated by intrinsically disordered regions of these enzymes. This review focuses on the biochemical and structural studies of the Y-family polymerases, which have provided clear insights into their function.

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Abbreviations

BRCT:

BRCA1 C-terminal

CTD:

C-terminal domain

NMR:

Nuclear magnetic resonance

PAD:

Polymerase-associated domain

PCNA:

Proliferating cell nuclear antigen

PIP:

PCNA-interacting protein

Pol:

Polymerase

RIR:

Rev1-interacting region

SAXS:

Small-angle X-ray scattering

TT:

Thymine–thymine

UBM:

Ubiquitin-binding motif

UBZ:

Ubiquitin-binding zinc finger

UV:

Ultraviolet

XPV:

Xeroderma pigmentosum variant form

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Acknowledgment

This article was supported by Award Number GM081433 from the National Institute of General Medical Sciences to M.T.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health.

We thank Christine Kondratick, Maria Spies, Adrian Elcock, and Marc Wold for valuable discussions.

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Authors and Affiliations

  1. Department of Biochemistry, University of Iowa College of Medicine, 4-403 Bowen Science Building, Iowa City, IA, 52242-1109, USA

    John M. Pryor, Lynne M. Dieckman, Elizabeth M. Boehm & M. Todd Washington

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  1. John M. Pryor
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  2. Lynne M. Dieckman
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  3. Elizabeth M. Boehm
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  4. M. Todd Washington
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Correspondence to M. Todd Washington .

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  1. Dept. of Biochem. and Mol. Biology, The Pennsylvania State University, University Park, Pennsylvania, USA

    Katsuhiko S. Murakami

  2. Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Michael A. Trakselis

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Pryor, J.M., Dieckman, L.M., Boehm, E.M., Washington, M.T. (2014). Eukaryotic Y-Family Polymerases: A Biochemical and Structural Perspective. In: Murakami, K., Trakselis, M. (eds) Nucleic Acid Polymerases. Nucleic Acids and Molecular Biology, vol 30. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-39796-7_4

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