生化2014 c15 dna damage and repair.ppt
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1、Biochemistry,Dept. of Biochemistry and Molecular Biology,Professor Wu Yaosheng 2014-05,DNA damage and repair,Chapter Fifteen,Case One,Why?,Xeroderma pigmentosum, XP,Section 1 DNA Damage,Section 2 DNA Repair,Section 3 Significance of DNA Damage and Repair,4,Main Contents,DNA damage;the factors to ind
2、uce DNA damage,Types of DNA damage:structural failure;mismatch;breakage;covalent linkage;,Manner of DNA repair:direct repair;excision repair;recombinant repair; translesion repair,5,Key Points,Questions,1. What is the relationship between DNA correct replication and DNA mutation?,4. Whether local sp
3、ace ultraviolet disinfection used commonly in clinical also can be used for disinfection on the surface of human body? Why is that?,3. Pickled fish hot pot is delicious, but whether is it fit to be often eaten? Why is that?,2.Why could DNA generate damage?,6,5.Which one of DNA damage repair mechanis
4、ms in human body is the most effective? Why?,The changes of DNA composition and structure caused by various factors in vivo or in vitro is called as DNA damage,1.DNA mutation, permanent alteration of DNA structure 2. The function of DNA as replication or transcription template is lost,The results in
5、duced by DNA damage :,7,Biological diversity dependent on:,DNA mutation,DNA repair,Balance,8,DNA Damage,Section One,1. DNA damage are caused by different mechanisms,1.1 Factors in vivo,DNA replication error DNA itself instability Reactive oxygen generated by metabolism in vivo,10,DNA replication err
6、ors,Interconversion of base pair during DNA replication, imbalance of dNTP concentration Rate of mismatch of DNA replication is about 1/1010 Missing or insertion of DNA fragment Alteration of copy number of repeat sequence, especially short tandem repeat sequence,11,遗传性脊髓小脑型共济失调3型(SCA3),Case Two,Fig
7、 1 Spinocerebellar ataxia type3 GXPL01 pedigree (CGA repeat),12,Spinocerebellar ataxia type 3 (SCA3) , MachadoJoseph disease (MJD),遗传性脊髓小脑型共济失调3型(SCA3),Case Two,13,Spinocerebellar ataxia type 3 (SCA3) , MachadoJoseph disease (MJD),DNA itself instability:,DNA itself structure instability is the most
8、frequent and important factor to cause DNA spontaneous damage When DNA is heated or environment pH changes, DNA molecular glycosidic bond between base and ribose can hydrolyze spontaneously, leading to the loss of base or fall off, of which the most occur depurination. Spontaneously deamination, fro
9、m one base to another base, for example, C to U, A to I, so on.,14,1.2 Factors in vitro,Physical factors Chemical factors Biological factors,Physical factors:ionization radiation, ultraviolet( UV),16,Chemical factors:,DNA damage induced by free radical DNA damage caused by base analogue DNA damage g
10、enerated by base repair reagent, alkylate reagent DNA damage induced by embed dye,17,DNA damage caused by physical & chemical factors,18,2. The types of DNA damage,Fall off of base (depurination) Damage of base structure Formation of pyrimidine dimer Breakage of single strand DNA or double strand DN
11、A DNA covalent linkage,19,Base damage and glycosyl damage,Base natures would be altered through group (radical) modification by some chemical toxicant Instable bases on DNA strands would be generated due to the damage of base or glycosyl, resulting in the breakage of DNA strands,20,Mismatch between
12、base pair:,Induced by insertion of base analogue, or action by base repair reagent Spontaneous base mismatch during DNA replication Thymine is replaced by uracil inserting in DNA,21,Breakage of DNA strands:,Caused by ionizing radiation, chemical toxicant, breakage of phosphodiester bond, deoxyribose
13、 damage, fall off or damage of base Local denaturation of DNA by base damage or glycosyl group and formation of sensitive site to nuclease, resulting in the breakage of DNA strands The formation of apurinic-apyrimidinic site, AP site, or abasic site by DNA glycosylase, breakage of DNA at the AP site
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