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。
Download pathway image as PDF
Canonical Non-Homologous End-Joining
PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide):
This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010].
更多...
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)):
ATM (Ataxia Telangiectasia Mutated):
TRIM29 (Tripartite Motif Containing 29):
ATR (Ataxia Telangiectasia and Rad3 Related):
H2AFX - H2A Histone Family, Member X:
XRCC4 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 4):
LIG4 - Ligase IV, DNA, ATP-Dependent:
NHEJ1 - Nonhomologous End-Joining Factor 1:
APTX - Aprataxin:
APLF (Aprataxin and PNKP Like Factor):
DCLRE1C (DNA Cross-Link Repair 1C):
PNKP (Polynucleotide Kinase 3'-Phosphatase):
DNTT - Deoxynucleotidyltransferase, terminal:
POLL (Polymerase (DNA Directed), lambda):
POLM - Polymerase (DNA Directed), mu:
MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):
RAD50 (RAD50 Homolog (S. Cerevisiae)):
TP53BP1 (Tumor Protein P53 Binding Protein 1):
Microhomology-Mediated End-Joining
PARP1 (Poly (ADP-Ribose) Polymerase 1):
This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery...
更多...
LIG3 (Ligase III, DNA, ATP-Dependent):
LIG2 - Ligase II, DNA, ATP-Dependent:
PARP2 - Poly (ADP-Ribose) Polymerase 2:
LIG1 (Ligase I, DNA, ATP-Dependent):
ATM (Ataxia Telangiectasia Mutated):
TRIM29 (Tripartite Motif Containing 29):
ATR (Ataxia Telangiectasia and Rad3 Related):
RBBP8 - Retinoblastoma Binding Protein 8:
MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):
RAD50 (RAD50 Homolog (S. Cerevisiae)):
RECQL2 - RECQL2 (ARABIDOPSIS RECQ HELICASE L2), 3'-5' DNA Helicase/ ATP-Dependent Helicase/ Four-Way Junction Helicase/ Protein Binding:
Homologous Recombination
RAD51 (DNA Repair Protein Homolog 1):
The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of...
更多...
BRCA1 (Breast Cancer 1):
BRCA2 (Breast Cancer 2, Early Onset):
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):
ATM (Ataxia Telangiectasia Mutated):
TRIM29 (Tripartite Motif Containing 29):
ATR (Ataxia Telangiectasia and Rad3 Related):
Rad51B - RAD51 Homolog B (S. Cerevisiae):
RAD51C (RAD51 Homolog C (S. Cerevisiae)):
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):
BARD1 (BRCA1 Associated RING Domain 1):
RBBP8 - Retinoblastoma Binding Protein 8:
FAM175A - Family with Sequence Similarity 175, Member A:
UIMC1 - Ubiquitin Interaction Motif Containing 1:
MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):
RAD50 (RAD50 Homolog (S. Cerevisiae)):
TP53BP1 (Tumor Protein P53 Binding Protein 1):
RPA1 - Replication Protein A1, 70kDa:
RPA2 (Replication Protein A2, 32kDa):
RPA3 (Replication Protein A3, 14kDa):
PALB2 (Partner and Localizer of BRCA2):
TOP3A (Topoisomerase (DNA) III alpha):
RMI1 (Homolog of Yeast RecQ-mediated Genome Instability 1):
RMI2 (RMI2, RecQ Mediated Genome Instability 2, Homolog (S. Cerevisiae)):
DNA2 (DNA Replication Helicase 2 Homolog (Yeast)):
RECQL2 - RECQL2 (ARABIDOPSIS RECQ HELICASE L2), 3'-5' DNA Helicase/ ATP-Dependent Helicase/ Four-Way Junction Helicase/ Protein Binding:
RAD54L (RAD54-Like (S. Cerevisiae)):
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
(MSH2):
ERCC1 (Excision Repair Cross Complementing Polypeptide-1):
MSH3 (MutS Homolog 3 (E. Coli)):
ERCC4 - Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 4:
ATM (Ataxia Telangiectasia Mutated):
TRIM29 (Tripartite Motif Containing 29):
ATR (Ataxia Telangiectasia and Rad3 Related):
MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):
RAD50 (RAD50 Homolog (S. Cerevisiae)):
RPA1 - Replication Protein A1, 70kDa:
RPA2 (Replication Protein A2, 32kDa):
RPA3 (Replication Protein A3, 14kDa):
RAD52 (RAD52 Homolog (S. Cerevisiae)):
Break-Induced Replication
MCM2 - Minichromosome Maintenance Complex Component 2
MCM7 - Minichromosome Maintenance Complex Component 7
RAD51 (DNA Repair Protein Homolog 1):
MRE11A - MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae):
RAD50 (RAD50 Homolog (S. Cerevisiae)):
RPA1 - Replication Protein A1, 70kDa:
RPA2 (Replication Protein A2, 32kDa):
RPA3 (Replication Protein A3, 14kDa):
MCM3 (Minichromosome Maintenance Complex Component 3):
MCM4 (Minichromosome Maintenance Deficient 4):
MCM5 - Minichromosome Maintenance Complex Component 5:
MCM6 - Minichromosome Maintenance Complex Component 6:
Base Excision Repair
OGG1 (8-Oxoguanine DNA Glycosylase):
This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the...
更多...
UNG (Uracil-DNA Glycosylase):
APEX1 - APEX Nuclease (Multifunctional DNA Repair Enzyme) 1
MPG - N-Methylpurine-DNA Glycosylase:
SMUG1 - Single-Strand-Selective Monofunctional Uracil-DNA Glycosylase 1:
TDG - Thymine-DNA Glycosylase:
MBD4 (Methyl-CpG Binding Domain Protein 4):
MUTYH - MutY Homolog (E. Coli):
NEIL1 (Endonuclease VIII-Like 1):
NEIL2 (Nei Endonuclease VIII-Like 2 (E. Coli)):
NEIL3 (Nei Endonuclease VIII-Like 3 (E. Coli)):
POLB (Polymerase (DNA Directed), beta):
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):
FEN1 (Flap Structure-Specific Endonuclease 1):
LIG1 (Ligase I, DNA, ATP-Dependent):
Nuleotide Excision Repair
POLR2B - Polymerase (RNA) II (DNA Directed) Polypeptide B, 140kDa
This gene encodes the second largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit, in combination with at least two other polymerase subunits, forms a structure within the polymerase that maintains contact in the active site of the enzyme between the DNA template and the newly synthesized RNA. [provided by RefSeq, Jul 2008].
更多...
XPC (Xeroderma Pigmentosum, Complementation Group C):
DDB1 (Damage Specific DNA Binding Protein 1):
XPA (Xeroderma Pigmentosum, Complementation Group A):
RAD23A (RAD23 Homolog A (S. Cerevisiae)):
RAD23B - RAD23 Homolog B (S. Cerevisiae):
CETN2 (Centrin, EF-Hand Protein, 2):
DDB2 (Damage-Specific DNA Binding Protein 2, 48kDa):
ERCC1 (Excision Repair Cross Complementing Polypeptide-1):
ERCC2 (Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 2):
ERCC3 - DNA Repair Protein Complementing XP-B Cells:
GTF2H1 - General Transcription Factor IIH, Polypeptide 1, 62kDa:
GTF2H4 (General Transcription Factor IIH, Polypeptide 4, 52kDa):
GTF2H3 (General Transcription Factor IIH, Polypeptide 3, 34kD):
GTF2H5 - General Transcription Factor IIH, Polypeptide 5:
CDK7 (Cyclin-Dependent Kinase 7):
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:
ERCC5 - DNA Repair Protein Complementing XP-G Cells:
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)):
PCNA (Proliferating Cell Nuclear Antigen):
XRCC1 (X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 1):
FEN1 (Flap Structure-Specific Endonuclease 1):
LIG1 (Ligase I, DNA, ATP-Dependent):
RPA1 - Replication Protein A1, 70kDa:
RPA2 (Replication Protein A2, 32kDa):
RPA3 (Replication Protein A3, 14kDa):
Mismatch Repair
(MSH2):
This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012].
更多...
MSH3 (MutS Homolog 3 (E. Coli)):
MSH6 (MutS Homolog 6 (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:
PCNA (Proliferating Cell Nuclear Antigen):
LIG1 (Ligase I, DNA, ATP-Dependent):
RPA1 - Replication Protein A1, 70kDa:
RPA2 (Replication Protein A2, 32kDa):
RPA3 (Replication Protein A3, 14kDa):
EXO1 - Exonuclease 1:
Direct Reversal
MGMT (O6-Methylguanine-DNA-Methyltransferase):
Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a
更多...
ALKBH - AlkB, Alkylation Repair Homolog 1 (E. Coli)
ALKBH2 - AlkB, Alkylation Repair Homolog 2
ALKBH3 - AlkB, Alkylation Repair Homolog 3 (E. Coli):
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:
PCNA (Proliferating Cell Nuclear Antigen):
You are here: