HOME

TheInfoList



OR:

DNA polymerase IV is a
prokaryotic A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...
polymerase A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using ba ...
that is involved in
mutagenesis Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using ...
and is encoded by the ''dinB'' gene. It exhibits no 3′→5′
exonuclease Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3′ or the 5′ end occurs. Its close relative is th ...
(proofreading) activity and hence is error prone. In ''E. coli'', DNA polymerase IV (Pol 4) is involved in non-targeted mutagenesis. Pol IV is a Family Y polymerase expressed by the ''dinB'' gene that is switched on via SOS induction caused by stalled polymerases at the replication fork. During SOS induction, Pol IV production is increased tenfold and one of the functions during this time is to interfere with Pol III holoenzyme processivity. This creates a checkpoint, stops replication, and allows time to repair DNA lesions via the appropriate repair pathway. Another function of Pol IV is to perform translesion synthesis at the stalled replication fork like, for example, bypassing N2-deoxyguanine adducts at a faster rate than transversing undamaged DNA. Cells lacking ''dinB'' gene have a higher rate of mutagenesis caused by DNA damaging agents.


Replication bypass of 8-oxoguanine

Reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () ...
are produced continuously during normal metabolism and these damage DNA. DNA polymerase IV can catalyze translesion synthesis across a variety of DNA damages including 8-oxoguanine, a major oxidative damage with high mutagenic potential. Upon
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
duplication by replicative polymerases, unrepaired 8-oxoguanine tends to mispair with A, so that during the next round of replication a G:C to T:A transversion mutation is produced (G:C → 8-oxoG:C → 8-oxoG:A → T:A). However, when DNA polymerase IV intervenes to bypass the damage, it preferentially incorporates the correct nucleotide CTP opposite 8-oxoguanine with high efficiency, thus avoiding potential mutations (G:C → 8-oxoG:C → 8-oxoG:C → GC).


References

{{Portal bar, Biology, border=no DNA replication EC 2.7.7