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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

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)):

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

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...

LIG2 - Ligase II, DNA, ATP-Dependent:

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):

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...

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 (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):

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):

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:

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

MCM7 - Minichromosome Maintenance Complex Component 7

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

RPA3 (Replication Protein A3, 14kDa):

MCM3 (Minichromosome Maintenance Complex Component 3):

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...

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

MBD4 (Methyl-CpG Binding Domain Protein 4):

NEIL2 (Nei Endonuclease VIII-Like 2 (E. Coli)):

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

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...

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:

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

(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)):

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

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

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

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

Trans-Lesion Synthesis

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

REV1 (REV1, Polymerase (DNA Directed)):

POLK - Polymerase (DNA Directed) kappa:

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