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38          SECTION II    BIOCHEmISTRY  ``BIOCHEMISTRY—MOlECUlAR                                                                                                     BIOCHEmISTRY  ``BIOCHEMISTRY—MOlECUlAR





               DNA replication       Eukaryotic DNA replication is more complex than in prokaryotes but uses many enzymes analogous to
                                       those listed below. In both prokaryotes and eukaryotes, DNA replication is semiconservative, involves
                                       continuous and discontinuous (Okazaki fragment) synthesis, and occurs in the 5′ Ž 3′ direction.
                Origin of            Particular consensus sequence in genome   AT-rich sequences (such as TATA box regions)
                 replication  A        where DNA replication begins. May be single   are found in promoters and origins of
                                       (prokaryotes) or multiple (eukaryotes).  replication.

                Replication fork  B    Y-shaped region along DNA template where
                                      leading and lagging strands are synthesized.
                Helicase  C          Unwinds DNA template at replication fork.   Helicase Halves DNA.
                                                                               Deficient in Bloom syndrome (BLM gene
                                                                                mutation).
                Single-stranded      Prevent strands from reannealing.
                 binding proteins  D
                DNA                  Create a single- or double-stranded break in the   In eukaryotes: irinotecan/topotecan inhibit
                 topoisomerases  E    helix to add or remove supercoils.        topoisomerase (TOP) I, etoposide/teniposide
                                                                                inhibit TOP II.
                                                                               In prokaryotes: fluoroquinolones inhibit TOP II
                                                                                (DNA gyrase) and TOP IV.
                Primase  F           Makes an RNA primer on which DNA
                                      polymerase III can initiate replication.
                DNA polymerase III  G   Prokaryotes only. Elongates leading strand   DNA polymerase III has 5′ Ž 3′ synthesis and
                                      by adding deoxynucleotides to the 3′ end.   proofreads with 3′ Ž 5′ exonuclease.
                                      Elongates lagging strand until it reaches   Drugs blocking DNA replication often have a
                                      primer of preceding fragment.             modified 3′ OH, thereby preventing addition of
                                                                                the next nucleotide (“chain termination”).
                DNA polymerase I  H   Prokaryotes only. Degrades RNA primer;   Same functions as DNA polymerase III, also
                                      replaces it with DNA.                     excises RNA primer with 5′ Ž 3′ exonuclease.
                DNA ligase  I        Catalyzes the formation of a phosphodiester   Joins Okazaki fragments.
                                      bond within a strand of double-stranded DNA.  Ligase Links DNA.
                Telomerase           Eukaryotes only. A reverse transcriptase (RNA-  Often dysregulated in cancer cells, allowing
                                      dependent DNA polymerase) that adds DNA   unlimited replication.
                                      (TTAGGG) to 3′ ends of chromosomes to avoid  Telomerase TAGs for Greatness and Glory.
                                      loss of genetic material with every duplication.

                                                       E                       G                           3'
                                                       Topoisomerase           DNA polymerase III            5'
                                                                C                                            A
                                                                Helicase                                    Origin of replication
                                                                                                  Leading strand
                                                                          B
                                                                         Replication fork              Lagging strand  3'
                                                                                            Okazaki fragment
                                                           D                                                         5'
                                         A
                       Area of interest                    Single-stranded       RNA primer
                                         Origin of replication  binding protein
                     Leading strand              Lagging strand                                                   I
                                                                   F                                             DNA ligase
                                                                   Primase
                                 Fork      Fork
                                 movement  movement
                                                                            G
                                                                            DNA polymerase III
                     Lagging strand              Leading strand                                  H
                                                                                                DNA polymerase I








          FAS1_2019_01-Biochem.indd   38                                                                                11/7/19   3:16 PM
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