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DNA Damage Repair

DNA是合成任意生物的基因信息的载体。DNA中修复的基因编码对于亚细胞放大可见的过程和生物总体功能至关重要。尽管如此,DNA一直受到内来源的损伤,比如:水解、氧化、烷基化或复制错误。另外,电离辐射、紫外线辐射和过多的化学试剂已经成为威胁DNA完整性的外部因素。

与RNA和蛋白不一样的是,DNA受损后不能降解重新合成。而是存在多种修复途径来确保DNA仍然保持完好。在1974年,弗朗西斯·克里克注意到“在DNA修复中,我们完全漏掉了酶可能的作用。我后来意识到DNA很珍贵,因此有可能存在多种不同的机制。

到今天这个预言还是适用:参与到DNA修复途径复杂的网络中后,一百多个基因被表征。DNA损伤可以通过六种不同的途径修复,这取决于损伤的类型:化学改性、未合并的核苷酸,通过直接反转(DR)、错配修复(MMR)和核苷酸切除修复机制反转交联。DNA单链断裂通过基本切除修复改善。高诱变DNA双链断裂最后通过多种复杂的途径修复,这些途径依赖于姐妹染色单体(在细胞周期S或G2阶段)的同源重组(HR)或双链断裂两端的非同源末端接合(NHEJ)。在DNA损伤不能及时修复的情况下,专门的DNA聚合酶启动跨损伤合成(TLS),从而防止DNA复制叉停止。造成这些修复途径的组件不工作的突变会导致疾病,比如:着色性干皮病、共济失调毛细血管扩张、范科尼贫血和患癌症的倾向。

另外,对于目前通常利用细胞DNA修复机制的靶向基因组编辑方法来说,这些修复机制受到高度关注。

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Canonical Non-Homologous End-Joining

XRCC6 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 6):

XRCC5 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 5 (Double-Strand-Break Rejoining)):

TRIM29 (Tripartite Motif Containing 29):

ATR (Ataxia Telangiectasia and Rad3 Related):

XRCC4 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 4):

APLF (Aprataxin and PNKP Like Factor):

POLL (Polymerase (DNA Directed), lambda):

POLM - Polymerase (DNA Directed), mu:

MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):

Microhomology-Mediated End-Joining

Homologous Recombination

POLE (Polymerase (DNA Directed), Epsilon, Catalytic Subunit):

POLE2 - Polymerase (DNA Directed), epsilon 2 (p59 Subunit):

POLE3 - Polymerase (DNA Directed), epsilon 3 (p17 Subunit):

POLE4 (Polymerase (DNA-Directed), epsilon 4 (p12 Subunit)):

POLD1 (Polymerase (DNA Directed), delta 1, Catalytic Subunit 125kDa):

POLD2 (Polymerase (DNA Directed), delta 2, Accessory Subunit):

POLD3 - Polymerase (DNA-Directed), delta 3, Accessory Subunit:

POLD4 (Polymerase (DNA-Directed), delta 4, Accessory Subunit):

TRIM29 (Tripartite Motif Containing 29):

ATR (Ataxia Telangiectasia and Rad3 Related):

Rad51B - RAD51 Homolog B (S. Cerevisiae):

RAD51C (DNA Repair Protein RAD51 Homolog 3):

XRCC2 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 2):

XRCC3 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 3):

BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1):

RBBP8 - Retinoblastoma Binding Protein 8:

FAM175A - Family with Sequence Similarity 175, Member A:

MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):

RPA3 (Replication Protein A3, 14kDa):

PALB2 (Partner and Localizer of BRCA2):

TOP3A (Topoisomerase (DNA) III alpha):

RMI2 (RMI2, RecQ Mediated Genome Instability 2, Homolog (S. Cerevisiae)):

DNA2 (DNA Replication Helicase 2 Homolog (Yeast)):

MUS81 (MUS81 Endonuclease Homolog (S. Cerevisiae)):

SLX1B - SLX1 Structure-Specific Endonuclease Subunit Homolog B (S. Cerevisiae):

BTBD12 - BTB (POZ) Domain Containing 12:

GEN1 (Gen Endonuclease Homolog 1 (Drosophila)):

Single Strand Annealing

MSH3 (MutS Homolog 3 (E. Coli)):

ERCC4 (Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 4):

TRIM29 (Tripartite Motif Containing 29):

ATR (Ataxia Telangiectasia and Rad3 Related):

MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):

RPA3 (Replication Protein A3, 14kDa):

Break-Induced Replication

MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):

MCM7 - Minichromosome Maintenance Complex Component 7:

RPA3 (Replication Protein A3, 14kDa):

Base Excision Repair

SMUG1 (Single-Strand-Selective Monofunctional Uracil-DNA Glycosylase 1):

MBD4 (Methyl-CpG Binding Domain Protein 4):

POLD1 (Polymerase (DNA Directed), delta 1, Catalytic Subunit 125kDa):

POLD2 (Polymerase (DNA Directed), delta 2, Accessory Subunit):

POLD3 - Polymerase (DNA-Directed), delta 3, Accessory Subunit:

POLD4 (Polymerase (DNA-Directed), delta 4, Accessory Subunit):

Nuleotide Excision Repair

POLR2B - Polymerase (RNA) II (DNA Directed) Polypeptide B, 140kDa:

RAD23A (RAD23 Homolog A (S. Cerevisiae)):

ERCC2 (Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 2):

ERCC3 - DNA Repair Protein Complementing XP-B Cells:

GTF2H4 (General Transcription Factor IIH, Polypeptide 4, 52kDa):

GTF2H3 (General Transcription Factor IIH, Polypeptide 3, 34kD):

GTF2H5 - General Transcription Factor IIH, Polypeptide 5:

RFC1 - Replication Factor C (Activator 1) 1, 145kDa:

RFC2 (Replication Factor C (Activator 1) 2, 40kDa):

RFC3 - Replication Factor C (Activator 1) 3, 38kDa:

RFC4 (Replication Factor C (Activator 1) 4, 37kDa):

RFC5 (Replication Factor C (Activator 1) 5, 36.5kDa):

POLK - Polymerase (DNA Directed) kappa:

ERCC4 (Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 4):

ERCC6 (Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 6):

ERCC8 (Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 8):

POLE (Polymerase (DNA Directed), Epsilon, Catalytic Subunit):

POLE2 - Polymerase (DNA Directed), epsilon 2 (p59 Subunit):

POLE3 - Polymerase (DNA Directed), epsilon 3 (p17 Subunit):

POLE4 (Polymerase (DNA-Directed), epsilon 4 (p12 Subunit)):

XRCC1 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 1):

RPA3 (Replication Protein A3, 14kDa):

Mismatch Repair

MSH3 (MutS Homolog 3 (E. Coli)):

MLH1 (MutL Homolog 1, Colon Cancer, Nonpolyposis Type 2 (E. Coli)):

PMS2 (PMS2 Postmeiotic Segregation Increased 2 (S. Cerevisiae)):

RFC1 - Replication Factor C (Activator 1) 1, 145kDa:

RFC2 (Replication Factor C (Activator 1) 2, 40kDa):

RFC3 - Replication Factor C (Activator 1) 3, 38kDa:

RFC4 (Replication Factor C (Activator 1) 4, 37kDa):

RFC5 (Replication Factor C (Activator 1) 5, 36.5kDa):

POLD1 (Polymerase (DNA Directed), delta 1, Catalytic Subunit 125kDa):

POLD2 (Polymerase (DNA Directed), delta 2, Accessory Subunit):

POLD3 - Polymerase (DNA-Directed), delta 3, Accessory Subunit:

RPA3 (Replication Protein A3, 14kDa):

Direct Reversal

Trans-Lesion Synthesis

POLI - Polymerase (DNA Directed) iota:

POLH - Polymerase (DNA Directed), eta:

REV3L (REV3-Like, Polymerase (DNA Directed), Zeta, Catalytic Subunit):

REV1 (REV1, Polymerase (DNA Directed)):

POLK - Polymerase (DNA Directed) kappa:

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