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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
  • collections(4)
Cat. No. ABIN6924015
Quantity 100 μL
Price $259.09
Reactivity Human
Validations
  • collections(2)
  • (1)
Cat. No. ABIN673434
Quantity 100 μL
Price $374.00
Reactivity Human
Validations
  • collections(4)
Cat. No. ABIN655900
Quantity 400 μL
Price $434.50
Reactivity Human, Rat
Validations
  • (2)
  • collections(8)
Cat. No. ABIN1724946
Quantity 0.1 mg
Price $468.60
Reactivity Human, Mouse, Rat
Validations
  • (3)
  • collections(15)
Cat. No. ABIN2854788
Quantity 100 μL
Price $509.08
Reactivity Human, Mouse
Validations
  • (4)
  • collections(8)
Cat. No. ABIN2854762
Quantity 100 μL
Price $509.08
Reactivity Human
Validations
  • (1)
  • collections(6)
Cat. No. ABIN6146634
Quantity 100 μL
Price $589.88
Reactivity Human
Validations
  • collections(3)
Cat. No. ABIN6940661
Quantity 100 μg
Price $591.12
Reactivity Human
Validations
  • collections(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)):

ATR (Ataxia Telangiectasia and Rad3 Related):

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

POLL (Polymerase (DNA Directed), lambda):

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):

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):

TOP3A (Topoisomerase (DNA) III alpha):

DNA2 (DNA Replication Helicase 2 Homolog):

BTBD12 (BTB (POZ) Domain Containing 12):

Single Strand Annealing

MSH3 (MutS Homolog 3):

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

ATR (Ataxia Telangiectasia and Rad3 Related):

Break-Induced Replication

MCM7 (Minichromosome Maintenance Complex Component 7):

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):

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):

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):

Mismatch Repair

MSH3 (MutS Homolog 3):

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):

Direct Reversal

Trans-Lesion Synthesis

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

FA/BRCA Pathway

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

BTBD12 (BTB (POZ) Domain Containing 12):

FAN1 (FANCD2/FANCI-Associated Nuclease 1):

FANCM (Fanconi Anemia Complementation Group M):

FANCE (Fanconi Anemia, Complementation Group E):

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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