| Autor: |
Trakselis MA; Department of Chemistry and Biochemistry, Baylor University , Waco, Texas 76798, United States., Cranford MT; Department of Chemistry and Biochemistry, Baylor University , Waco, Texas 76798, United States., Chu AM; Department of Chemistry and Biochemistry, Baylor University , Waco, Texas 76798, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
Chemical research in toxicology [Chem Res Toxicol] 2017 Nov 20; Vol. 30 (11), pp. 1956-1971. Date of Electronic Publication: 2017 Sep 22. |
| DOI: |
10.1021/acs.chemrestox.7b00190 |
| Abstrakt: |
The ability for DNA polymerases (Pols) to overcome a variety of obstacles in its path to maintain genomic stability during replication is a complex endeavor. It requires the coordination of multiple Pols with differing specificities through molecular control and access to the replisome. Although a number of contacts directly between Pols and accessory proteins have been identified, forming the basis of a variety of holoenzyme complexes, the dynamics of Pol active site substitutions remain uncharacterized. Substitutions can occur externally by recruiting new Pols to replisome complexes through an "exchange" of enzyme binding or internally through a "switch" in the engagement of DNA from preformed associated enzymes contained within supraholoenzyme complexes. Models for how high fidelity (HiFi) replication Pols can be substituted by translesion synthesis (TLS) Pols at sites of damage during active replication will be discussed. These substitution mechanisms may be as diverse as the number of Pol families and types of damage; however, common themes can be recognized across species. Overall, Pol substitutions will be controlled by explicit protein contacts, complex multiequilibrium processes, and specific kinetic activities. Insight into how these dynamic processes take place and are regulated will be of utmost importance for our greater understanding of the specifics of TLS as well as providing for future novel chemotherapeutic and antimicrobial strategies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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