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Overview of the Steps Leading to Translesion Synthesis

A recent study showed that Pol IV binds the (1-clamp to help release a stalled Pol III from the same (1-clamp, leaving Pol IV/(l-clamp at the site of the lesion [101], This process is rapid (t 15 s). Presumably, this mechanism operates for each translesion synthesis DNA polymerase (II, IV and V), all of which have [Pg.359]

P-clamp binding sites (consensus QLxLx) that are required for them to be active in E. coli [102]. An X-ray crystal structure shows that the underlined amino acids OLVLGL at the C-terminus of Pol IV form the main interactions with a pocket in the P-clamp [103]. The a-subunit of Pol III and the 8-subunit of the y-complex also bind to the same site on the P-clamp. In vitro studies show that the P-clamp stimulates both polymerase activity and processivity of translesion synthesis DNA polymerases the addition of P-clamp in vitro increases Pol IV activity around 2000-fold and processivity from 1 to around 400 nucleotides, and also increases Pol V activity around 100-fold and processivity from 1-2 to around 18 nucleotides [71]. [Pg.360]

What factors affect the choice about which translesion synthesis DNA polymerase will insert opposite a particular lesion Several lines of evidence suggest that E. coli has a hierarchy for the replication of normal, unadducted DNA when Pol III is inactivated Pol II IV V [104]. (The assays did not permit an assessment of Pol I.) Since this order (III II IV V) does not reflect the relative concentration of these DNA polymerases in cells (see above), another mechanism for decision making was suggested, such as relative DNA polymerase affinity for the P-clamp. This order does reflect relative fidelity of these DNA polymerases and would be a sensible order for E. coli to allow translesion synthesis DNA polymerases to initially sample adducts/lesions prior to a decision about which polymerase will perform translesion synthesis. However, the ultimate decision is probably predominantly controlled by which translesion synthesis DNA polymerase is most efficient at bypassing a particular adduct/lesion biochemically. [Pg.360]

After insertion opposite the lesion, additional extension synthesis by a translesion synthesis DNA polymerase is required or else Pol Ill s proofreading 3 -5 exonuclease activity will remove the inserted nucleotides back to the site of the lesion [69, 72]. The amount of extension required for Pol III to resume normal synthesis is pathway-dependent, being [L + 4] for the AAF-C8-dG nonmutagenic pathway with Pol V and [L + 3] for the AAF-C8-dG -2 frameshift pathway with Pol V [69, 72], [Pg.360]

More is known about translesion synthesis of the major adduct of AAF and N2-dG adducts in E. coli than any other adducts/lesions, as outlined in this section. [Pg.360]


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