F部分DNA损伤，修复和重组 .pptVIP

Transcription-coupled repair（转录偶联修复） Tc1/mariner因子 Tc1/mariner因子是真核细胞中最常见的转座子。 结构简单，仅包含一段末端反向重复序列(inverted terminal repeat，ITR)和编码转座酶的基因，采用“剪切粘贴”的转座机制进行转移。但是此类转座子的转座酶大都在漫长的进化中失活。 1997年Ivics根据积累的系统发生数据，利用生物信息学的方法，对鱼类当中Tcl类转座酶的基因序列进行分子重建，使这个失活了一千多万年的基因恢复了转座活性。 这个转座系统因而得名“睡美人” (Sleeping Beauty, SB)”。 与其他转座系统的效率相比，“睡美人”在脊椎动物中的转座效率最高。 F2-4 Bulky adduct （大块加合物） DNA lesions that distort the double helix and cause localized denaturation, for example pyrimidine dimers（嘧啶二聚体） and arylating agents agents（芳香族烷化剂） These lesions disrupt the normal function of the DNA. Cyclobutane pyrimidine dimer(嘧啶二聚体) Guanine adduct of benzo[a]pyrene Aromatic arylating agents （芳香族烷化剂） Covalent adducts DNA lesions (DNA损害） Oxidative damage (氧化损伤） Alkylation (烷基化作用） Bulky adducts (聚加化合物） Occurs under Normal condition Increased by ionizing radiation (physical mutagens) Alkylating agents (Chemical mutagens) UV light (physical mutagens) Carcinogen（致癌物） (Chemical mutagens) F2 DNA damage F3 DNA repair Photoreactivation (光复活) Alkyltransferase (烷基转移酶) Exision repair (切除修复) Mismatch repair (错配修复) F3-1: Photoreactivation（光复活） Monomerization of cyclobutane pyrimidine dimers（环丁烷嘧啶二聚体） by DNA photolyases（光解酶） in the presence of visible light Direct reversal of a lesion and is error-free F3-2: Alkyltransferase（烷基转移酶） Direct reversal of a lesion and is error-free Removes the alkyl group from mutagenic O6-alkylguanine which can base-pair with T. The alkyl group is transferred to the protein itself and inactivate it. The response is adaptive（适应性的） because it is induced in E. coli by low levels of alkylating agents and gives increased protection against the lethal and mutagenic effects of the high doses F3-3: Excision repair（切除修复） Includes nucleotide excision repair (核苷酸切除修复，NER) and base excision repair (碱基切除修复，BER). Is a ubiquitous mechanism repairing a variety of lesions. Error-free repair Nucleotide excision repair An endonuclease cleaves DNA a precise number of bases on both sides of