Kinetic Basis of Nucleotide Selection Employed by a Protein Template-dependent DNA Polymerase

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2010 Jun 4

PMID 20518555

Citations 22

Authors

Jessica A Brown

Jason D Fowler

Zucai Suo

Affiliations

Soon will be listed here.

Abstract

Rev1, a Y-family DNA polymerase, contributes to spontaneous and DNA damage-induced mutagenic events. In this paper, we have employed pre-steady-state kinetic methodology to establish a kinetic basis for nucleotide selection by human Rev1, a unique nucleotidyl transferase that uses a protein template-directed mechanism to preferentially instruct dCTP incorporation. This work demonstrated that the high incorporation efficiency of dCTP is dependent on both substrates: an incoming dCTP and a templating base dG. The extremely low base substitution fidelity of human Rev1 (10(0) to 10(-5)) was due to the preferred misincorporation of dCTP with templating bases dA, dT, and dC over correct dNTPs. Using non-natural nucleotide analogues, we showed that hydrogen bonding interactions between residue R357 of human Rev1 and an incoming dNTP are not essential for DNA synthesis. Lastly, human Rev1 discriminates between ribonucleotides and deoxyribonucleotides mainly by reducing the rate of incorporation, and the sugar selectivity of human Rev1 is sensitive to both the size and orientation of the 2'-substituent of a ribonucleotide.

Citing Articles

The Catalytic Activity of Human REV1 on Undamaged and Damaged DNA.

Stolyarenko A, Novikova A, Shilkin E, Poltorachenko V, Makarova A Int J Mol Sci. 2024; 25(7).

PMID: 38612916 PMC: 11012841. DOI: 10.3390/ijms25074107.

Mechanism of nucleotide discrimination by the translesion synthesis polymerase Rev1.

Weaver T, Click T, Khoang T, Washington M, Agarwal P, Freudenthal B Nat Commun. 2022; 13(1):2876.

PMID: 35610266 PMC: 9130138. DOI: 10.1038/s41467-022-30577-0.

DNA Polymerase η Promotes the Transcriptional Bypass of -Alkyl-2'-deoxyguanosine Adducts in Human Cells.

Tan Y, Guo S, Wu J, Du H, Li L, You C J Am Chem Soc. 2021; 143(39):16197-16205.

PMID: 34555898 PMC: 8751221. DOI: 10.1021/jacs.1c07374.

One, No One, and One Hundred Thousand: The Many Forms of Ribonucleotides in DNA.

Nava G, Grasso L, Sertic S, Pellicioli A, Muzi Falconi M, Lazzaro F Int J Mol Sci. 2020; 21(5).

PMID: 32131532 PMC: 7084774. DOI: 10.3390/ijms21051706.

Current perspectives on mechanisms of ribonucleotide incorporation and processing in mammalian DNA.

Sassa A, Yasui M, Honma M Genes Environ. 2019; 41:3.

PMID: 30700998 PMC: 6346524. DOI: 10.1186/s41021-019-0118-7.

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