中北大学DNA-damage--repair-and-recombination.pptVIP

4．DNA damage, repair and recombination Including 4.1 Mutagenesis 4.2 DNA damage 4.3 DNA repair 4.4 DNA Recombination 4.5 DNA Transposition 4.1 Mutagenesis 4.1.1 Mutation 4.1.2 Physical mutagens 4.1.3 Chemical mutagens 4.1.1 Mutation Mutations are permanent, heritable alterations in the base sequence of the DNA. Piont mutation — a single base change. Transition (转换) – one purine (or pyrimidine ) is replaced by the other Transversion（颠换）-- a purine replaces a pyrimidine or vice versa Silent – no effect on the amino acid incorporated into a protein. Missense mutation –an altered amino acid in a gene product. Nonsense mutation – generate new stop codons. Frameshift mutation – the translated protein sequence is changed completely 4.1.2 Physical mutagens Ionizing radiation – x-rays, γ-rays causes the target molecules to lose electrons – strand break of base and sugar destruction Noninonizing – causes molecular viberations of promotion of electrons to higher energy levels --- lead to the formation of new chemical bonds. UV light – pyrimidine dimers 4.1.3 Chemical mutagens Base analogs 碱基类似物– alter base pairing properties--direct Nitrous acid 亚硝酸– deaminates(脱胺基) C to produce U Alkylating agents 烷化剂, Arylating agents 芳基化剂 4.2 DNA damage DNA lesions损伤– an alteration to the normal chemical or physical structure of the DNA. Oxidative damage – reactive oxygen species 活性氧自由基 can attack the DNA and produce oxidation products (p94 Fig1) Alkylating agents 烷化剂-- Methylmethane sulfonate (MMS)甲基磺酸甲酯; Ethylnitrosourea (ENU)乙基亚硝基脲 Bulky adducts大型化合物--are DNA lesions generated in response to environmental agents including benzo[a]pyrene (苯并[a]芘) and solar ultraviolet radiation. 4.3 DNA repair 4.3.1 Excision repair（切除修复） Nucleotide excision repair (NER): an endonulcease (核酸内切酶) cleaves the DNA and an oligonucleotide(寡核苷酸) is removed leaving a gap. Base excision repair (BER): modified bases are recognized by DNA glycosylases (糖苷水解酶), which cleav