Lecture:10 The Central Dogma of Molecular Biology Dr.Q.M.I.Haq

The Central Dogma of Molecular Biology First proposed by Francis Crick (1958) He said that the sequence involved in the expression of hereditary characteristics is: The Central Dogma involves three major players, namely DNA, RNA, and proteins. It also involves three processes, namely DNA replication, transcription, and translation through protein synthesis. It forms the basis of storage, transmission, and expression of hereditary information.

The Central Dogma of Molecular Biology

DNA Replication The DNA duplication. The transfer the genetic information from a parent to a daughter cell. The DNA base sequences are precisely copied.

unwinds part of DNA helix Replication: 1st step Unwind DNA helicase enzyme unwinds part of DNA helix stabilized by single-stranded binding proteins Replication: 2nd step Build daughter DNA strand add new complementary bases DNA polymerase III Replication Adding bases can only add nucleotides to 3 end of a growing DNA strand need a “starter” nucleotide to bond to strand only grows 53

Leading & Lagging strands Okazaki Limits of DNA polymerase III can only build onto 3 end of existing DNA strand 5 Okazaki fragments 5 5  3 5 3 5 3 ligase Lagging strand 3 growing replication fork 3 5 Leading strand 3  5 Lagging strand Okazaki fragments joined by ligase “spot welder” enzyme 3 DNA polymerase III Leading strand continuous synthesis

Telomeres RNA primer built by primase serves as starter sequence for DNA polymerase III DNA polymerase I removes sections of RNA primer and replaces with DNA nucleotides Telomeres Repeating, non-coding sequences at the end of chromosomes = protective cap Telomerase enzyme extends telomeres different level of activity in different cells

editing, repair & primer removal DNA polymerases Roger Kornberg 2006 DNA polymerase III 1000 bases/second! main DNA builder DNA polymerase I 20 bases/second editing, repair & primer removal Arthur Kornberg 1959 In 1953, Kornberg was appointed head of the Department of Microbiology in the Washington University School of Medicine in St. Louis. It was here that he isolated DNA polymerase I and showed that life (DNA) can be made in a test tube. In 1959, Kornberg shared the Nobel Prize for Physiology or Medicine with Severo Ochoa — Kornberg for the enzymatic synthesis of DNA, Ochoa for the enzymatic synthesis of RNA.

Matthew Meselsson and Franklin Stahl DNA Replication (SEMICONSERVATIVE and SEMIDISCONTINOUS) 2 old strands It is SEMICONSERVATIVE or the 2 old strands will serve as the template for the formation of 2 new strands. It is SEMIDISCONTINOUS or the new strands formed are attached by fragments (Okazaki fragments). 1 new strand 1 old strand Matthew Meselsson and Franklin Stahl

Example of DNA Replication 5’ TAC CGG AAT GCA ATG CAT ATG 3’ OLD 3’ ATG GCC TTA CGT TAC GTA TAC 5’ OLD 3’ ATG GCC TTA CGT TAC GTA TAC 5’ NEW 5’ TAC CGG AAT GCA ATG CAT ATG 3’ NEW

Large team of enzymes coordinates replication DNA Replication Large team of enzymes coordinates replication Enzymes more than a dozen enzymes & other proteins participate in DNA replication