1. Introduction to Molecular Genetics http://priede.bf.lu.lv/http://priede.bf.lu.lv/ Studiju materiāli / MolekularasBiologijas / Ievads MolGen / EN

2. MUTATION – a permanent (heritable) change in the DNA sequence Genetic STABILITY Genetic CHANGES SIN o temporary o permanent o somatic o germline o spontaneous (background) o induced o DNA replication o chemical factors o physical factors o transposons, viruses o neutral o functional - coding sequences - regulatory regions - loss-of-function - gain-of-function - bad and lethal - adaptive

3. Single base changes (point mutations) transitions transversions Molecular Biology of the Gene, 5th Edition The most frequent types of mutations Insertions / Deletions Changes in the number of simple sequence repeats Vogel and Motulsky’s Human Genetics, 4th Edition; modified.

4. Cells make large investments in DNA repair Molecular Biology of the Gene, 5th Edition

5. Replication is highly accurate, but not perfect Molecular Biology of the Gene, 5th Edition

6. Eukaryotes MISMATCH REPAIR corrects replication errors

7. Some replication errors still escape detection: MUTATION Molecular Biology of the Gene, 5th Edition MUTATION REPLICATION ERROR (still can be repaired) (a permanent change; can not be repaired)

9. hydrolatic attack oxidative damage uncontrolled methylation DNA frequently suffers from spontaneous alterations and chemical damage

10. Depurination and deamination are the most frequent spontaneous chemical reactions causing DNA damage

11. UV induces the formation of pyrimidine dimers

12. If uncorrected, these changes may result in mutations

13. Molecular Biology of the Gene, 5th Edition Some damages can be repaired through simple reversal, eg, photoreactivation of pyrimidine dimers by DNA photolyase

14. Base Excision Repair and Nucleotide Excision Repair are the two major pathways for repairing DNA damage

15. Two distinct mechanisms repair double-strand breaks

16. Molecular Biology of the Cell, 5th Edition (modified)

17. CANCER is a disease of genetic changes

18. RECOMBINATION Homologous (or general) –between two homologous DNA sequences Site-Specific –between two defined DNA sequence elements Transposition –between specific DNA element and any DNA site

19. Homologous recombination repairs strand breaks

20. Homologous recombination is crucial for meiosis Molecular Biology of the cell, 5th Edition

21. Homologous recombination is crucial for meiosis and creates new combinations of alleles IZOMERIZATION OF A HOLLIDAY JUNCTION

22. Homologous recombination in meiosis may result in Gene Conversion

23. Gene conversion by mismatch repair

24. Modern Genetic Analysis Bacteria have no sex, yet they have several ways for receiving genes from other bacteria

25. Bacterial viruses (bacteriophages) reproduce by a lytic or a lysogenic cycle Phage – temperate Bacteria – lysogenic Life The Science of Biology, 7th Edition

26. Lysogenic cycle involves integration of phage into the host chromosome by SITE-SPECIFIC RECOMBINATION Molecular Biology of the Gene, 5th Edition

27. The insertion of bacteriophage genome into the host DNA (recombination sites) (recombinase)

28. Site-specific recombination is mediated by specific sequences Molecular Biology of the Gene, 5th Edition

29. Types of site-specific recombination Molecular Biology of the Gene, 5th Edition the darker red and blue boxes – the recombinase recognition sequences the black arrows – the crossover regions recombination sites

30. Unlike elements moving by site-specific recombination, TRANSPOSONS can insert into any DNA sequence Molecular Biology of the Gene, 5th Edition (transposon)

31. Molecular Biology of the Gene, 5th Edition Transposons can move with or without duplication

32. There are three principal classes of transposable elements Molecular Biology of the Gene, 5th Edition (LTR retrotransposons or elements) P - promoter LTR - long terminal repeat RT - reverse transcriptase UTR – untranslated region ORF - open reading frame (nonviral retrotransposons) ORF 2 = RT and endonuclease (DNA-only transposons)

33. The ‘cut-and-paste’ transposition of DNA transposons (synaptic complex)

34. Bacterial transposons often carry antibiotic resistance genes

35. RETROTRANSPOSITION involves RNA intermediate Genomes, 2nd Edition

36. Molecular Biology of the Gene, 5th Edition Retrotransposition of LTR elements cDNA – copy DNA – DNA that has been made by reverse transcription from RNA

37. The life cycle of a retrovirus

38. Content of transposons differs among different organisms Molecular Biology of the Gene, 5th Edition

39. Transposons (mainly – retrotransposons) occupy nearly half of the human genome

40. The genetic basis of antibody diversity

41. Antibody diversity is based on unusual composition of immunoglobulin genes and the V(D)J recombination

42. The V(D)J recombination pathway Molecular Biology of the Gene, 6th Edition recombinases

43. We have arrived at the GENE EXPRESSION GENE EXPRESSION Molecular Biology of the Gene, 6th Edition