Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

Gergely N. Nagy, Ibolya Leveles, B. Vértessy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The occurrence of modified bases in DNA is attributed to some major factors: incorporation of altered nucleotide building blocks and chemical reactions or radiation effects on bases within the DNA structure. Several enzyme families are involved in preventing the incorporation of noncanonical bases playing a 'sanitizing' role. The catalytic mechanism of action of these enzymes has been revealed for a number of representatives in clear structural and kinetic detail. In this review, we focus in detail on those examples where clear evidence has been produced using high-resolution structural studies. Comparing the protein fold and architecture of the enzyme active sites, two main classes of sanitizing deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are distinguished by the site of nucleophilic attack. In enzymes associated with attack at the α-phosphorus, it is shown that coordination of the γ-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the β-phosphorus atom mainly coordinate the α- and the β-phosphate only. Characteristic differences are also observed with respect to the role of the metal ion cofactor (Mg(2+) ) and the coordination of nucleophilic water. Using different catalytic mechanisms embedded in different protein folds, these enzymes present a clear example of convergent evolution.

Original languageEnglish
Pages (from-to)4207-4223
Number of pages17
JournalFEBS Journal
Volume281
Issue number18
DOIs
Publication statusPublished - Sep 1 2014

Fingerprint

Nucleosides
DNA Repair
Repair
DNA
Enzymes
Phosphorus
Phosphates
Pyrophosphatases
Deoxyribonucleosides
Radiation effects
Radiation Effects
Metal ions
triphosphoric acid
Chemical reactions
Catalytic Domain
Proteins
Nucleotides
Metals
Ions
Atoms

Keywords

  • DNA repair
  • non-canonical nucleotides
  • NTPases
  • nucleophilic attack
  • X-ray crystallography

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool. / Nagy, Gergely N.; Leveles, Ibolya; Vértessy, B.

In: FEBS Journal, Vol. 281, No. 18, 01.09.2014, p. 4207-4223.

Research output: Contribution to journalArticle

Nagy, Gergely N. ; Leveles, Ibolya ; Vértessy, B. / Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool. In: FEBS Journal. 2014 ; Vol. 281, No. 18. pp. 4207-4223.
@article{770d6dd835c04ee3a9e22bac134c91d7,
title = "Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool",
abstract = "The occurrence of modified bases in DNA is attributed to some major factors: incorporation of altered nucleotide building blocks and chemical reactions or radiation effects on bases within the DNA structure. Several enzyme families are involved in preventing the incorporation of noncanonical bases playing a 'sanitizing' role. The catalytic mechanism of action of these enzymes has been revealed for a number of representatives in clear structural and kinetic detail. In this review, we focus in detail on those examples where clear evidence has been produced using high-resolution structural studies. Comparing the protein fold and architecture of the enzyme active sites, two main classes of sanitizing deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are distinguished by the site of nucleophilic attack. In enzymes associated with attack at the α-phosphorus, it is shown that coordination of the γ-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the β-phosphorus atom mainly coordinate the α- and the β-phosphate only. Characteristic differences are also observed with respect to the role of the metal ion cofactor (Mg(2+) ) and the coordination of nucleophilic water. Using different catalytic mechanisms embedded in different protein folds, these enzymes present a clear example of convergent evolution.",
keywords = "DNA repair, non-canonical nucleotides, NTPases, nucleophilic attack, X-ray crystallography",
author = "Nagy, {Gergely N.} and Ibolya Leveles and B. V{\'e}rtessy",
year = "2014",
month = "9",
day = "1",
doi = "10.1111/febs.12941",
language = "English",
volume = "281",
pages = "4207--4223",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "18",

}

TY - JOUR

T1 - Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

AU - Nagy, Gergely N.

AU - Leveles, Ibolya

AU - Vértessy, B.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - The occurrence of modified bases in DNA is attributed to some major factors: incorporation of altered nucleotide building blocks and chemical reactions or radiation effects on bases within the DNA structure. Several enzyme families are involved in preventing the incorporation of noncanonical bases playing a 'sanitizing' role. The catalytic mechanism of action of these enzymes has been revealed for a number of representatives in clear structural and kinetic detail. In this review, we focus in detail on those examples where clear evidence has been produced using high-resolution structural studies. Comparing the protein fold and architecture of the enzyme active sites, two main classes of sanitizing deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are distinguished by the site of nucleophilic attack. In enzymes associated with attack at the α-phosphorus, it is shown that coordination of the γ-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the β-phosphorus atom mainly coordinate the α- and the β-phosphate only. Characteristic differences are also observed with respect to the role of the metal ion cofactor (Mg(2+) ) and the coordination of nucleophilic water. Using different catalytic mechanisms embedded in different protein folds, these enzymes present a clear example of convergent evolution.

AB - The occurrence of modified bases in DNA is attributed to some major factors: incorporation of altered nucleotide building blocks and chemical reactions or radiation effects on bases within the DNA structure. Several enzyme families are involved in preventing the incorporation of noncanonical bases playing a 'sanitizing' role. The catalytic mechanism of action of these enzymes has been revealed for a number of representatives in clear structural and kinetic detail. In this review, we focus in detail on those examples where clear evidence has been produced using high-resolution structural studies. Comparing the protein fold and architecture of the enzyme active sites, two main classes of sanitizing deoxyribonucleoside triphosphate pyrophosphatases can be assigned that are distinguished by the site of nucleophilic attack. In enzymes associated with attack at the α-phosphorus, it is shown that coordination of the γ-phosphate group is also ensured by multiple interactions. By contrast, enzymes catalyzing attack at the β-phosphorus atom mainly coordinate the α- and the β-phosphate only. Characteristic differences are also observed with respect to the role of the metal ion cofactor (Mg(2+) ) and the coordination of nucleophilic water. Using different catalytic mechanisms embedded in different protein folds, these enzymes present a clear example of convergent evolution.

KW - DNA repair

KW - non-canonical nucleotides

KW - NTPases

KW - nucleophilic attack

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=84909971352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84909971352&partnerID=8YFLogxK

U2 - 10.1111/febs.12941

DO - 10.1111/febs.12941

M3 - Article

C2 - 25052017

AN - SCOPUS:84909971352

VL - 281

SP - 4207

EP - 4223

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 18

ER -