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Ribonucleotide Reductase Family - Genetics & Genomics (Hardcover)
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Ribonucleotide Reductase Family - Genetics & Genomics (Hardcover)
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Ribonucleotide reductase (RNR), a universal enzyme present in
essentially all living cells and organisms, has a central role in
DNA replication and repair by catalysing production of
deoxyribonucleotides from the corresponding ribonucleotides. Three
major classes of RNRs are known, differing in their cofactor
requirements: class I RNRs (with subclasses Ia and Ib) carry a
stable tyrosyl radical and are oxygen-dependent, class II RNRs
require the vitamin B12 cofactor 5'-deoxyadenosylcobalamin and are
oxygen-independent, and class III RNRs carry a stable glycyl
radical and are oxygen-sensitive. Despite these differences, all
classes have a similar reaction mechanism and the same highly
specific catalytic core structure, indicating that they evolved
from a common ancestor. Biochemical studies of RNRs from selected
model organisms in combination with the vast number of deduced RNR
sequences from publicly available complete genomic sequences show
that whereas eukaryotes and their viruses with few exceptions
contain only class Ia RNRs, all three major RNR classes are found
among prokaryotes and bacteriophages and quite often one organism
encodes more than one class of RNR. They are compiled in an open
access database, called RNRdb for Ribonucleotide Reductase database
that is available at http://rnrdb.molbio.su.se. RNRs are produced
in a strictly controlled way depending upon growth phase and
environmental cues. The authors describe a comprehensive summary of
how the expression of RNR genes is regulated in several eubacterial
organisms and in yeast. Due to RNR's importance for the realisation
of DNA replication, it has been recognised as a possible target for
antiproliferative therapy. The authors present a comprehensive
summary of RNR-specific inhibitors that have reached clinical
trials and/or are currently used in clinical therapy.
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