同济大学：《细胞的生物化学》课程电子教案（PPT课件）Genetic information transfer——DNA biosynthesis（DNA replication-复制）

Objectives After completion of this section,you should be able to 1.Understand the central dogma and general principles of DNA replication. 2.List molecules involved in DNA replication 3.Describe the process of DNA replication 4.List types of DNA damage 5.Explain mechanism of DNA repair (BER and NER) 6.Appreciate other ways of replication and reverse transcription (in telomere)

Objectives After completion of this section, you should be able to : 1. Understand the central dogma and general principles of DNA replication. 2. List molecules involved in DNA replication 3. Describe the process of DNA replication 4. List types of DNA damage 5. Explain mechanism of DNA repair (BER and NER) 6. Appreciate other ways of replication and reverse transcription (in telomere)

DNA replication is the most accurate biological process Fertilized egg(one cell) Camnegie Stages of Human Development 33 ~50,000,000,000,000 cell divisions

DNA replication is the most accurate biological process Fertilized egg (one cell) ~50,000,000,000,000 cell divisions

Defects in DNA replication genes and human disease At least 80 human diseases result from genetic mutations. At least 32 of these diseases result from mutations in genes encoding either DNA replication or repair proteins. Disease Affected Proteins Progressive external ophthalmoplegia (PEO) Mitochondrial DNA polymerase y Alpers syndrome Mitochondrial DNA polymerase Y Progressive extemal ophthaimoplegia(PEO) Mitochondrial DNA helicase Hereditary non-polyposis colorectal cancer Several DNA mismatch repair proteins (HNPCC).or Lynch syndrome Bloom syndrome DNA helicase Wemer syndrome DNA helicase Rothmund-Thomson syndrome DNA helicase Rapadillino Syndrome DNA helicase Xeroderma pigmentosum varant DNA polymerase n XP-Cockayne syndrome DNA helicase Trichothiodystrophy DNAhelicases LIG4 syndrome DNA ligase Miller-Dieker lissencephaly syndrome* Contiguous haploinsufficiency(-20 genes)including the gene for Replication Factor A (single-stranded DNA-binding protein) William Beuren syndrome' Contiguous haploinsuficiency(-24 genes)including the gene for a subunit of Replication Factor C(clamp loader) *syndromes that MAY be related to DNA replication or repair proteins

DNA replication is the process in which DNA serves as the template for its own synthesis.When Watson and Crick proposed the double helical base- paired model for DNA structure in 1953,the idea of a process in which parental DNA directs its own synthesis emerged. "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." J.D.Watson F.H.C.Crick, Nature1953,171,737-738

DNA replication is the process in which DNA serves as the template for its own synthesis. When Watson and Crick proposed the double helical base￾paired model for DNA structure in 1953, the idea of a process in which parental DNA directs its own synthesis emerged

Outline of the section 1.Basic concepts and general principles of DNA replication 2.Proteins involved in DNA replication 3.Biosynthesis process of DNA 4.DNA damage and repair

Outline of the section 1. Basic concepts and general principles of DNA replication 2. Proteins involved in DNA replication 3. Biosynthesis process of DNA 4. DNA damage and repair

Central dogma replication transcription translation DNA→RA→ Protein RNA replication reverse transcription

Central dogma replication DNA reverse transcription RNA Protein transcription translation RNA replication

DNA replication A reaction in which daughter DNAs are synthesized using the parental DNAs as the template. Genetic information is transmitted in high fidelity replication Complete and accurate Parental DNA Daughter DNA

DNA replication replication Parental DNA Daughter DNA  A reaction in which daughter DNAs are synthesized using the parental DNAs as the template.  Genetic information is transmitted in high fidelity Complete and accurate

The overall DNA synthesis reaction: (dNMP)n dNTP(dNMP)n+1 PPi DNA strand substrate elongated DNA strand Replication of both daughter strands proceeds by addition of nucleotide monomers in the 5'to 3'direction Template DNA 5 PP. DNA polymerase B1'B2'B3'B4'B5 B1'B2'B3'B4' B5 61B2B3 0H+ OH ...P attack OH 5→3 Replicated DNA Phosphodiester bond formation

 The overall DNA synthesis reaction: (dNMP)n + dNTP (dNMP)n+1 + PPi DNA strand substrate elongated DNA strand Phosphodiester bond formation attack Replication of both daughter strands proceeds by addition of nucleotide monomers in the 5’ to 3’ direction

Section1 Basic concepts and general principles of DNA replication

Section1 Basic concepts and general principles of DNA replication

1.General principles of DNA replication DNA replication is a process of Semi-conservative replication Semi-discontinuous replication Bidirectional replication High fidelity replication

§ 1. General principles of DNA replication DNA replication is a process of ⚫ Semi-conservative replication ⚫ Semi-discontinuous replication ⚫ Bidirectional replication ⚫ High fidelity replication