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DNA Damage Repair

Written/Edited by Dr. Stefan Pellenz, PhD

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:

  1. Aparicio, Baer, Gautier: "DNA double-strand break repair pathway choice and cancer." in: DNA repair, Vol. 19, pp. 169-75, (2015) (PubMed).
  2. Chatterjee, Walker: "Mechanisms of DNA damage, repair, and mutagenesis." in: Environmental and molecular mutagenesis, Vol. 58, Issue 5, pp. 235-263, (2017) (PubMed).
  3. Ray Chaudhuri, Nussenzweig: "The multifaceted roles of PARP1 in DNA repair and chromatin remodelling." in: Nature reviews. Molecular cell biology, Vol. 18, Issue 10, pp. 610-621, (2017) (PubMed).
  4. Bian, Meng, Zhang, Li: "MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment." in: Molecular cancer, Vol. 18, Issue 1, pp. 169, (2020) (PubMed).
  5. Fang, Wu, Zhang, Liu, Zhang: "Fanconi Anemia Pathway: Mechanisms of Breast Cancer Predisposition Development and Potential Therapeutic Targets." in: Frontiers in cell and developmental biology, Vol. 8, pp. 160, (2020) (PubMed).
  6. Burgess, Rose, Boucher, Plowman, Molloy, Fisher, O'Leary, Richard, O'Byrne, Bolderson: "The Therapeutic Potential of DNA Damage Repair Pathways and Genomic Stability in Lung Cancer." in: Frontiers in oncology, Vol. 10, pp. 1256, (2020) (PubMed).

Selected DNA Damage Repair Antibodies
Product
Reactivity
Validations
Cat. No.
Quantity
Price
Reactivity Human, Rat
Validations
  • (2)
  • (8)
Cat. No. ABIN1724946
Quantity 0.1 mg
Price $511.50
Reactivity Human
Validations
  • (4)
  • (16)
Cat. No. ABIN2854788
Quantity 100 μL
Price $609.18
Reactivity Human, Mouse
Validations
  • (4)
  • (8)
Cat. No. ABIN2854762
Quantity 100 μL
Price $609.18
Reactivity Human
Validations
  • (2)
  • (1)
Cat. No. ABIN673434
Quantity 100 μL
Price $384.62
Reactivity Human
Validations
  • (4)
Cat. No. ABIN655900
Quantity 400 μL
Price $429.00
Reactivity Human
Validations
  • (3)
Cat. No. ABIN6940661
Quantity 100 μg
Price $597.38
Reactivity Human
Validations
  • (3)
Cat. No. ABIN6972484
Quantity 100 μg
Price $705.69

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):

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):

RAD50 (RAD50 Homolog (S. Cerevisiae)):

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):

RAD50 (RAD50 Homolog (S. Cerevisiae)):

WRN - RECQL2:

Homologous Recombination

RAD51 (DNA Repair Protein Homolog 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):

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):

UIMC1 (Ubiquitin Interaction Motif Containing 1):

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):

DNA2 (DNA Replication Helicase 2 Homolog):

WRN - RECQL2:

MUS81 (MUS81 Endonuclease Homolog):

BTBD12 (BTB (POZ) Domain Containing 12):

GEN1 (Gen Endonuclease Homolog 1):

Single Strand Annealing

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):

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

Base Excision Repair

OGG1 (8-Oxoguanine DNA Glycosylase):

APEX1 (Apurinic/Apyrimidinic Endonuclease 1):

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

MBD4 (Methyl-CpG Binding Domain Protein 4):

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):

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):

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

MSH3 (MutS Homolog 3):

MSH6 (MutS Homolog 6 (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):

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):

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):

FANCE (Fanconi Anemia, Complementation Group E):

BLM (Bloom Syndrome RecQ Like Helicase):

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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