Abstract:
:Ribonucleotide reductase (RNR) is the enzyme critically responsible for the production of the 5'-deoxynucleoside-triphosphates (dNTPs), the direct precursors for DNA synthesis. The dNTP levels are tightly controlled to permit high efficiency and fidelity of DNA synthesis. Much of this control occurs at the level of the RNR by feedback processes, but a detailed understanding of these mechanisms is still lacking. Using a genetic approach in the bacterium Escherichia coli, a paradigm for the class Ia RNRs, we isolated 23 novel RNR mutants displaying elevated mutation rates along with altered dNTP levels. The responsible amino-acid substitutions in RNR reside in three different regions: (i) the (d)ATP-binding activity domain, (ii) a novel region in the small subunit adjacent to the activity domain, and (iii) the dNTP-binding specificity site, several of which are associated with different dNTP pool alterations and different mutational outcomes. These mutants provide new insight into the precise mechanisms by which RNR is regulated and how dNTP pool disturbances resulting from defects in RNR can lead to increased mutation.
journal_name
DNA Repair (Amst)journal_title
DNA repairauthors
Ahluwalia D,Bienstock RJ,Schaaper RMdoi
10.1016/j.dnarep.2012.02.001subject
Has Abstractpub_date
2012-05-01 00:00:00pages
480-7issue
5eissn
1568-7864issn
1568-7856pii
S1568-7864(12)00047-Xjournal_volume
11pub_type
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