1. 1.Structures and Functions of Nucleic Acids 2.Organization and Content of Genomes 3.DNA Replication 4.The Mutability and Repair of DNA 5.DNA Recombination 6.Transcription and RNA Processing 7.Translation 8.Regulation of Gene Expression 9.Techniques of Molecular Genetics 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