Role of DNA Polymerases in Repeat-Mediated Genome Instability

Role of DNA polymerases in repeat-mediated genome instability.

Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We analyzed the role of DNA polymerases in the instability of Friedreich's ataxia (GAA)(n) repeats in a yeast experimental system. The elementary step of expansion corresponded to ~160 bp in the wild-type strain, matching the size of Okazaki fragments in yeast. This step increased when DNA polymerase α was mutated, s...

Role of Accessory DNA Polymerases in DNA

DNA repair and trinucleotide repeat instability.

enes harboring certain trinucleotide repeat (TNR) sequences are at risk for high-frequency mutations that expand or contract the repeat tract. The triplet sequences CNG (where N = any nucleotide) and GAA are known to cause human disease when they expand by more than a few repeats in certain key genes. One of the crucial questions in the field is the mechanism (or, more likely, mechanisms) of tr...

Stress-induced modulators of repeat instability and genome evolution.

Evolution hinges on the ability of organisms to adapt to their environment. A key regulator of adaptability is mutation rate, which must be balanced to maintain genome fidelity while permitting sufficient plasticity to cope with environmental changes. Multiple mechanisms govern an organism's mutation rate. Constitutive mechanisms include mutator alleles that drive global, permanent increases in...

Role of DNA polymerases in excision repair in Escherichia coli.

The excision repair process following ultraviolet irradiation has been fractionated into its individual steps in toluene-treated cells. Incision can be examined in vitro independently of other reactions by omission of the deoxyribonucleoside triphosphates which prohibits repair synthesis and causes incisions to accumulate. Incision requires ATP, continues from 10 to 15 min at 37”, and is specif...