tailieunhanh - USMLE ROAD MAP BIOCHEMISTRY – PART 8

3 được mở rộng bởi DNA pol III. 6. Nhân rộng trên các sợi tụt hậu là không liên tục bởi vì polymerase chỉ có thể sao chép các khu vực sợi đơn có sẵn tại ngã ba và chỉ trong 5 '3' hướng. a. Một mồi RNA ngắn là lần đầu tiên được tổng hợp gần nhất kết thúc 3 của ngã ba bởi primase, mà thực sự là một DNA hướng RNA polymerase | 156 USMLE Road Map Biochemistry b. The nascent or growing polynucleotide chain being made as complement to the leading strand continuously provides a 3 end that is extended by DNA pol III. 6. Replication on the lagging strand is discontinuous because polymerases can only copy the single-stranded region available at the fork and only in the 5 to 3 direction. a. A short RNA primer is first synthesized nearest the 3 end of the fork by primase which is actually a DNA-directed RNA polymerase. b. DNA pol III binds to the primer-template end and extends the primer by adding deoxyribonucleotides during the elongation step. c. Short pieces of DNA called Okasaki fragments are made in this way and each fragment is completed when DNA pol III bumps up against the primer end of the previous fragment Figure 11-2 . d. The RNA primers are excised and simultaneously replaced with DNA by DNA pol I which also has 5 to 3 exonuclease activity. e. DNA ligase then seals the remaining nick by catalyzing formation of a phosphodiester bond with ATP as energy donor. INHIBITORS OF DNA REPLICATION AS ANTICANCER AND ANTIVIRAL AGENTS When nucleoside analogs such as cytosine arabinoside AraC azidothymidine zidovudine or AZT and dideoxyinosine ddI are converted into the corresponding nucleotides by salvage pathways they can be incorporated into nascent DNA strands by DNA polymerases. These compounds have modified sugars that are not capable of forming downstream phosphodiester bonds which blocks further elongation of the chains. Although these drugs effectively inhibit the replication of DNA in all cells they are highly toxic to rapidly proliferating cells such as cancer cells and cells infected by virus. C. Topoisomerases are responsible for relieving supercoils in the dsDNA that occur by twisting and fold-back as the DNA is unwound ahead of the replication fork. 1. If supercoils or superhelices were not removed they would eventually block movement of the replication fork by preventing further DNA