DNA Damage Repair
DNA is the carrier of the genetic information that defines any living being. The genetic code fixed in DNA is crucial for processes on a subcellular scale up to the appearance and function of the organism as s whole. Nonetheless, DNA is constantly exposed to insults from endogenous sources such as hydrolysis, oxidation, alkylation, or replication errors. In addition, ionizing radiation, UV radiation, and a plethora of chemical reagents are external factors that threaten the integrity of DNA.
Unlike RNA and proteins, DNA is not being degraded and re-synthesized upon damage. Instead, various repair pathways are in existence to assure that the DNA remains intact. Francis Crick noted in 1974 that “we totally missed the possible role of enzymes in [DNA] repair. I later came to realize that DNA is so precious that probably many distinct mechanisms could exist.”
This presage holds true today: over a hundred genes have been characterized since that are involved in an intricate network of DNA repair pathways. DNA damage can be repaired via six different pathways depending on the nature of the lesion: chemical modifications, misincorporated nucleotides, and cross-links are reverted through direct reversal (DR), mismatch repair (MMR), and nucleotide excision repair mechanisms. DNA single strand breaks are being mended via base excision repair. Highly mutagenic DNA double strand breaks finally are repaired through a number of complex pathways that rely on homologous recombination (HR) with the sister chromatid (in the S or G2 phase of the cell cycle) or non-homologous end-joining (NHEJ) of both ends of the double strand break. The Fanconi Anemia pathway is or particular importance for the repair of DNA interstrand crosslinks. In case a DNA lesion cannot be repaired in time, specialized DNA polymerases enable trans-lesion synthesis (TLS) in order to prevent the DNA replication fork from stalling. Mutations that render components of these repair pathways non-functional lead to diseases such as xeroderma pigmentosum, ataxia telangiectasia, Fanconi anemia, and a predisposition for cancer.
Besides, these repair mechanisms are of high interest for current targeted genome editing approaches that typically take advantage of the cellular DNA repair machinery.
Related pathways:
References:
- Aparacio T et al. DNA double-strand break repair pathway choice and cancer. DNA Repair (2014) PMID 24746645
- Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen (2017) PMID 28485537
- Chaudhuri AR, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol (2017) PMID 28676700
- Bian L et al. MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment. Mol Cancer (2019) PMID 31767017
- Fang C et al. Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets. Front Cell Dev Biol (2020) PMID 32300589
- Burgess JT et al. The Therapeutic Potential of DNA Damage Repair Pathways and Genomic Stability in Lung Cancer. Front Oncol (2020) PMID 32850380
Selected DNA Damage Repair Antibodies
Product
Reactivity
Validations
Cat. No.
Quantity
Price
Reactivity
Human
Validations
- (4)
Cat. No.
ABIN6924015
Quantity
100 μL
Price
$259.09
Reactivity
Human
Validations
- (2)
- (1)
Cat. No.
ABIN673434
Quantity
100 μL
Price
$374.00
Reactivity
Human
Validations
- (4)
Cat. No.
ABIN655900
Quantity
400 μL
Price
$434.50
Reactivity
Human, Rat
Validations
- (2)
- (8)
Cat. No.
ABIN1724946
Quantity
0.1 mg
Price
$468.60
Reactivity
Human, Mouse, Rat
Validations
- (3)
- (15)
Cat. No.
ABIN2854788
Quantity
100 μL
Price
$509.08
Reactivity
Human, Mouse
Validations
- (4)
- (8)
Cat. No.
ABIN2854762
Quantity
100 μL
Price
$509.08
Reactivity
Human
Validations
- (1)
- (6)
Cat. No.
ABIN6146634
Quantity
100 μL
Price
$589.88
Reactivity
Human
Validations
- (3)
Cat. No.
ABIN6940661
Quantity
100 μg
Price
$591.12
Reactivity
Human
Validations
- (3)
Cat. No.
ABIN6972484
Quantity
100 μg
Price
$620.28
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)):
PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide):
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):
POLL (Polymerase (DNA Directed), lambda):
POLM (Polymerase (DNA Directed), mu):
MRE11A - Mre11:
RAD50 (RAD50 Homolog (S. Cerevisiae)):
NBN - Nibrin:
TP53BP1 (Tumor Protein P53 Binding Protein 1):
Microhomology-Mediated End-Joining
PARP1 (Poly (ADP-Ribose) Polymerase 1):
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:
RAD50 (RAD50 Homolog (S. Cerevisiae)):
NBN - Nibrin:
WRN - RECQL2:
Homologous Recombination
RAD51 (DNA Repair Protein Homolog 1):
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:
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):
BARD1 (BRCA1 Associated RING Domain 1):
RBBP8 - Retinoblastoma Binding Protein 8:
FAM175A - CCDC98:
UIMC1 (Ubiquitin Interaction Motif Containing 1):
MRE11A - Mre11:
RAD50 (RAD50 Homolog (S. Cerevisiae)):
NBN - Nibrin:
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):
DNA2 (DNA Replication Helicase 2 Homolog):
WRN - RECQL2:
RAD54L (RAD54-Like):
MUS81 (MUS81 Endonuclease Homolog):
SLX1B - SLX1A/GIYD2:
BTBD12 (BTB (POZ) Domain Containing 12):
GEN1 (Gen Endonuclease Homolog 1):
Single Strand Annealing
MSH2 (Mismatch Repair Protein 2):
ERCC1 (Excision Repair Cross Complementing Polypeptide-1):
MSH3 (MutS Homolog 3):
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:
RAD50 (RAD50 Homolog (S. Cerevisiae)):
NBN - Nibrin:
RPA1 (Replication Protein A1, 70kDa):
RPA2 (Replication Protein A2, 32kDa):
RPA3 (Replication Protein A3, 14kDa):
RAD52 (RAD52 Homolog (S. Cerevisiae)):
Break-Induced Replication
MRE11A - Mre11:
RAD50 (RAD50 Homolog (S. Cerevisiae)):
MCM2 (Minichromosome Maintenance Complex Component 2):
MCM7 (Minichromosome Maintenance Complex Component 7):
RAD51 (DNA Repair Protein Homolog 1):
NBN - Nibrin:
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):
UNG (Uracil-DNA Glycosylase):
APEX1 (Apurinic/Apyrimidinic Endonuclease 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 (Endonuclease 8-like 2):
NEIL3 (Nei Endonuclease VIII-Like 3):
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):
XPC (Xeroderma Pigmentosum, Complementation Group C):
DDB1 (Damage Specific DNA Binding Protein 1):
XPA (Xeroderma Pigmentosum, Complementation Group A):
RAD23A (RAD23 Homolog A):
RAD23B (RAD23 Homolog B):
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 (Mismatch Repair Protein 2):
MSH3 (MutS Homolog 3):
MSH6 (MutS Homolog 6 (E. Coli)):
MLH1 (MutL Homolog 1):
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):
ALKBH1 (AlkB, Alkylation Repair Homolog 1):
ALKBH2 (AlkB, Alkylation Repair Homolog 2):
ALKBH3 (AlkB, Alkylation Repair Homolog 3):
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):
FA/BRCA Pathway
BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1):
ERCC1 (Excision Repair Cross Complementing Polypeptide-1):
BTBD12 (BTB (POZ) Domain Containing 12):
FAN1 (FANCD2/FANCI-Associated Nuclease 1):
CHEK1 (Checkpoint Kinase 1):
FANCI (Fanconi Anemia Complementation Group I):
FANCA (Fanconi Anemia Group A Protein):
FANCG (Fanconi Anemia Complementation Group G):
FANCM (Fanconi Anemia Complementation Group M):
BRCA2 (Breast Cancer 2, Early Onset):
HES1 (Hes Family bHLH Transcription Factor 1):
FANCE (Fanconi Anemia, Complementation Group E):
BLM (Bloom Syndrome RecQ Like Helicase):
BRCA1 (Breast Cancer 1):
FANCL (Fanconi Anemia, Complementation Group L):
EIF2AK2 (Eukaryotic Translation Initiation Factor 2-alpha Kinase 2):
FANCC (Fanconi Anemia, Complementation Group C):
FANCD2 (Fanconi Anemia, Complementation Group D2):
FANCF (Fanconi Anemia, Complementation Group F):
FANCB (Fanconi Anemia, Complementation Group B):
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