These structures can potentially block progression of the replication fork and cause intra- or inter-molecular template switching of DNA polymerase between the inverted elements [15], [19].
One approach towards overcoming these limitations is to block progression of the viral replication cycle at an earlier stage than normally occurs with MVA infection.
67– 70 Unrepaired lesions (particularly bulky adducts, intercalations, crosslinks, and helix distortions) can block progression of the replication fork.
At a dose of 8.1 mg/kg, NITD609 exhibited a potent (but not total) ability to inhibit transmission from mouse to mosquito and completely blocked progression of the life cycle to subsequent mice with a single dose.
Although endogenous and environmentally induced DNA damage is primarily removed by DNA repair mechanisms (including nucleotide excision repair, base excision repair, mismatch repair, and various forms of strand break repair), some damage may remain, which can block progression of the normal DNA replication machinery.
As shown with anti-oestrogens [ 17], these data are consistent with the hypothesis that aromatase inhibitors such as letrozole induce regression of breast cancer in vivo by simply blocking progression of cells through the cell cycle rather than by a direct cytotoxic effect.
Thus, gp130 in hepatocytes seems an interesting therapeutic target for blocking progression of HCC.
"Our findings suggest potential strategies for using normal gut bacteria to block progression of insulin-dependent diabetes in kids who have high genetic risk," Dr. Danska added.
p21 blocks progression of the cell cycle at G1/S and is involved in G2/M phase arrest (Dulic et al, 1998).
These and other damaged bases, if not repaired, may have miscoding properties and lead to mutation upon replication or block progression of the replication fork (11 , 25.
