DNA Damage & Repair and its Therapeutic Potential

Eva Volckova

Eva Volckova
Oct 29, 2021 10:30:00 AM

Since DNA was first discovered by researchers, decades of work have been done to understand its importance as it is the code of life itself. While DNA is the cornerstone of life, it is not immune to damages, and as so it is vital for DNA to repair itself for normal cell function to be maintained. Though, DNA is not always able to repair itself and this leads to some diseases such as various cancers. Fortunately, DNA repair pathways are capable of being tools to provide therapies to combat these diseases.

 

dna dmage

Introduction to DNA Damage and Repair

Over the course of one day within the human body, there are thousands of instances of DNA damage that are the result of both endogenous and exogenous factors. Some examples of exogenous reasons for DNA damage are ultraviolet (UV) radiation from the sun and the chemicals from tobacco in cigarette smoke. On the other hand, endogenous DNA damage can occur from metabolic processes within the body. For example, one metabolic process can produce reactive oxygen which can damage DNA.

When enough DNA is damaged, apoptosis, a form of programmed cell death, can occur. Though, when there is no apoptotic control, DNA damage may result in cancer. An example of this is skin cancer which is caused by overexposure to UV rays from the sun, tanning beds, or sunlamps. In the short term, this damage can cause a sunburn but, over time, UV damage adds up. This leads to changes in skin texture, premature skin aging, and even skin cancer.

For these reasons, it is necessary to have a repair system for DNA. For as often as DNA damage is happening throughout the body, so is DNA repair. Some repair pathways repair double stranded DNA breaks, which is when both strands of the DNA have damage at the same location. Other repair pathways repair single stranded breaks, where only one DNA strand has missing or incorrect nucleotide(s).

Types of DNA Repair

Double stranded break repair:

  1. HR: Homologous repair
    • In HR, the homologous chromosome is used as a template to fix the damage. This pathway features the BRCA family.
  2. NHEJ: Non-homologous end joining
    • In NHEJ, the broken DNA strands are reconnected without any attempt to replace what was previously there.

Single stranded break repair:

  1. BER: base excision repair
    • In BER, the single stranded DNA break is fixed using the complementary DNA strand as a template. This pathway features the PARP family.
  2. NER: Nucleotide excision repair
    • The NER pathway also repairs single stranded DNA breaks by using the complementary DNA, however it repairs damage caused by ultraviolet light.
  3. MMR: DNA mismatch repair
    • MMR fixes incorrect nucleotide pairings in the DNA.

Cancer Treatment Using DNA Repair Pathways: PARP Inhibitors

BRCA1 and BRCA2 are important in homologous repair, and when they are mutated, cells can become cancerous. While the rate of breast cancer for women without BRCA1 or 2 mutations is 13%, a BRCA1 or 2 mutation increases the likelihood of developing breast cancer up to 45-72%.

When a cell loses its ability to undergo homologous repair and becomes cancerous, base excision repair (BER) becomes its primary method of DNA repair. Although there are other repair pathways, they are less reliable and more error prone. Therefore, if the BER pathway is inhibited, the BRCA-deficient cancer cell will not have a reliable repair system, and it will accumulate DNA damage that will trigger cell death.

One way to inhibit the BER pathway is through targeting a protein called PARP (poly-ADP ribose polymerase) which plays a vital role in BER. This can be done using a PARP inhibitor, which binds to PARP when it is on DNA to stop it from performing its function. PARP inhibitors are small molecules, and there are several currently on the market, such as olaparib, rucaparib, and talazoparib. The inhibition of PARP when it is bound to DNA will not only prevent single stranded DNA breaks from being fixed, but, it also causes PARP to be trapped on the DNA. Then, if the cell tries to replicate its DNA, the trapped PARP protein will be in the way, and a double stranded break will occur. This will drastically speed up the occurrence of DNA damage, and apoptosis of the cancer cell will occur. There are many other potential targets to utilize DNA repair pathways as cancer therapies.

Conclusion

Since DNA damage occurs constantly, it is vital for our cells to have a reliable DNA repair response. However, there are times when blocking a form of DNA repair is beneficial, such as when targeting certain types of cancer cells.

ABclonal offers a variety of antibodies, proteins, and ELISA kits covering DNA damage and repair. We have currently over 150 related antibodies with multiple applications in our inventory. ABclonal is committed to continued development of additional products involved in DNA damage and repair to meet the growing market demand.

Available Antibodies for DNA Damage and Repair Research
DNA Damage Sensors

Target Name

Cat.No.

Product Name

Applications

Reactivity

 

Mre11

A4222

Mre11 Rabbit mAb

WB

Human Mouse

A2559

MRE11A Rabbit pAb

WB IF IP

Human Mouse Rat

 

 

Rad50

A3869

Rad50 Rabbit mAb

WB

Human Mouse Rat

A3078

RAD50 Rabbit pAb

WB IHC IF IP

Human Mouse Rat

A0182

RAD50 Rabbit pAb

WB IHC IF

Human Mouse

 

Nbs1

A0783

[KO Validated] NBN Rabbit pAb

WB

Human Mouse

A4197

p95/NBS1 Rabbit mAb

WB

Human

 

 

Ku70

A11223

Ku70 Rabbit mAb

WB IHC IF

Human Mouse

A7330

KU70 Rabbit pAb

WB IHC IF IP

Human Mouse Rat

A0883

KU70 Rabbit pAb

WB IHC IF

Human Mouse Rat

 

Ku80

A12338

Ku80 Rabbit mAb

WB IHC IF

Human

A5862

XRCC5 Rabbit pAb

WB IHC IF IP

Human Mouse Rat

 

 

RPA

A0990

RPA1 Rabbit pAb

WB IF IP

Human, Mouse

A2189

RPA2 Rabbit pAb

WB IHC IF IP

Human, Mouse, Rat

A6721

RPA3 Rabbit pAb

WB IF

Human, Mouse, Rat

Rad9

A1890

RAD9A Rabbit pAb

WB IHC IF

Human Rat

Rad1

A1047

RAD1 Rabbit pAb

WB

Human Mouse

 

Hus1

A5407

HUS1 Rabbit pAb

WB IF IP

Human Mouse

A13938

HUS1 Rabbit pAb

WB IHC IF

Human Mouse Rat

 

 

 

 

 

H2A.X

A11412

Histone H2A.X Rabbit mAb

WB IHC

Human Mouse Rat

A11361

Histone H2AX Rabbit pAb

WB IHC IF

Human Mouse Rat

A11463

Histone H2AX Rabbit pAb

WB IF IP

Human Mouse Rat

AP0099

Phospho-γH2A.X-S139 Rabbit pAb

WB IHC IF

Human Mouse Rat

 

AP0687

Phospho-Histone H2AX-S139 Rabbit

mAb

 

WB IHC IF

 

Human Mouse Rat

 

DNA Damage Mediators

Target Name

Cat.No.

Product Name

Applications

Reactivity

53BP1

A5757

53BP1 Rabbit pAb

WB IHC IF

Human Mouse Rat

Claspin

A17202

CLSPN Rabbit pAb

WB

Human

Rad17

A5359

RAD17 Rabbit pAb

WB IF IP

Human

 

 

BRCA1

A11549

BRCA1 Rabbit pAb

WB IHC IF

Human Mouse Rat

A11318

BRCA1 Rabbit pAb

WB IHC IF

Human Mouse Rat

AP0232

Phospho-BRCA1-S1423 Rabbit pAb

WB IHC IF

Human Mouse Rat

TopBP1

A5781

TOPBP1 Rabbit pAb

WB IHC IF

Human Mouse

 

DNA Damage Signaling Kinases

Target Name

Cat.No.

Product Name

Applications

Reactivity

 

 

ATM

A19650

ATM Rabbit mAb

WB IHC

Human Mouse Rat

AP0008

Phospho-ATM-S1981 Rabbit pAb

WB IF

Human

AP1030

Phospho-ATM-S1981 Rabbit mAb

WB

Human

 

ATR

A7247

ATR Rabbit pAb

WB

Human

AP0676

Phospho-ATR-S428 Rabbit pAb

WB IF

Human Mouse

 

ATRIP

A7139

ATRIP Rabbit pAb

WB IP

Human Mouse

A5041

ATRIP Rabbit pAb

WB IF IP

Human

 

ATM/ATR substrate

 

AP0933

Phospho-(Ser/Thr) ATM/ATR Substrate

Rabbit pAb

 

WB

 

ALL

DNA-PK

A7716

PRKDC Rabbit pAb

WB IHC IF

Human Mouse

 

Cell Cycle Signaling Regulation

Target Name

Cat.No.

Product Name

Applications

Reactivity

 

 

 

 

 

 

 

 

 

Chk1/2

A7653

CHEK1 Rabbit pAb

WB IHC IF

Human Mouse Rat

AP0017

Phospho-CHEK1-S280 Rabbit pAb

WB IHC IF

Human Mouse Rat

AP0578

Phospho-CHEK1-S345 Rabbit pAb

WB

Human Mouse Rat

AP1047

Phospho-Chk1-S296 Rabbit mAb

WB

Human

A0466

CHEK2 Rabbit pAb

WB IHC IF IP

Human Mouse

A2145

CHEK2 Rabbit pAb

WB IF

Human

A19543

Chk2 Rabbit mAb

WB IHC

Human

AP0590

Phospho-CHEK2-T68 Rabbit pAb

WB

Human

RK05790

Phospho-CHEK2-S516 Antibody kit

 

 

 

 

 

Cdc25

A1173

CDC25A Rabbit pAb

WB IHC IF

Human Mouse Rat

A0534

CDC25B Rabbit pAb

WB

Human

A11328

CDC25C Rabbit pAb

WB IF

Human Mouse

AP0577

Phospho-cdc25C-S216 Rabbit pAb

WB

Human Rat

 

CDK

A11420

CDK1 Rabbit mAb

WB IHC IF

Human Mouse Rat

A0220

CDK1 Rabbit pAb

WB IHC IF

Human Mouse Rat

 

 

Cell Cycle Signaling Regulation
Target Name Cat.No. Product Name Applications Reactivity
Chk1/2 A7653 CHEK1 Rabbit pAb WB IHC IF Human Mouse Rat
AP0017 Phospho-CHEK1-S280 Rabbit pAb WB IHC IF Human Mouse Rat
AP0578 Phospho-CHEK1-S345 Rabbit pAb WB Human Mouse Rat
AP1047 Phospho-Chk1-S296 Rabbit mAb WB Human
A0466 CHEK2 Rabbit pAb WB IHC IF IP Human Mouse
A2145 CHEK2 Rabbit pAb WB IF Human
A19543 Chk2 Rabbit mAb WB IHC Human
AP0590 Phospho-CHEK2-T68 Rabbit pAb WB Human
RK05790 Phospho-CHEK2-S516 Antibody kit    
Cdc25 A1173 CDC25A Rabbit pAb WB IHC IF Human Mouse Rat
A0534 CDC25B Rabbit pAb WB Human
A11328 CDC25C Rabbit pAb WB IF Human Mouse
AP0577 Phospho-cdc25C-S216 Rabbit pAb WB Human Rat
CDK A11420 CDK1 Rabbit mAb WB IHC IF Human Mouse Rat
A0220 CDK1 Rabbit pAb WB IHC IF Human Mouse Rat
AP0016 Phospho-CDK1-Y15 Rabbit pAb WB IHC IF IP Human Mouse Rat
AP0324 Phospho-CDK1-T161 Rabbit pAb WB IHC IF IP Human Mouse
AP0015 Phospho-CDK1-T14 Rabbit pAb WB IF Human Mouse Rat
RK05747 Phospho-CDK1-T161 Antibody kit    
A0094 CDK2 Rabbit mAb WB Human Mouse Rat
AP1005 Phospho-Cdk2-Y15 Rabbit mAb WB Human Mouse
AP0325 Phospho-CDK2-T160 Rabbit pAb WB IHC Human
A11136 [KO Validated] Cdk4 Rabbit mAb WB IF Human
A0366 CDK4 Rabbit pAb WB IHC IF IP Human Mouse Rat
AP0593 Phospho-CDK4-T172 Rabbit pAb WB Human Mouse Rat
RK05753 Phospho-CDK4-T172 Antibody kit    
A19029 CDK5 Rabbit mAb WB Human Mouse Rat
A18080 [KO Validated] CDK5 Rabbit pAb WB IF Human Mouse Rat
A1545 [KO Validated] CDK6 Rabbit pAb WB IHC IF IP Human Mouse
A0106 CDK6 Rabbit mAb WB Human Rat
A12942 CDK7 Rabbit pAb WB IHC IF Human Mouse Rat
A9654 Cdk8 Rabbit mAb WB Human Mouse Rat
A11145 Cdk9 Rabbit mAb WB IHC IF IP Human Mouse Rat
A2690 CDK10 Rabbit pAb WB IHC IF Human Mouse
A12830 CDK11B Rabbit pAb WB IF Human Mouse
AP1138 Phospho-CDK1/2/3-T14 Rabbit mAb WB Human Mouse Rat
AP1001 Phospho-Cdk1/2-T14 Rabbit mAb WB Human Mouse Rat
Cyclin A19036 Cyclin A2 Rabbit mAb WB IHC IF Human Mouse Rat
A7632 Cyclin A2 Rabbit pAb WB IHC IF Human Mouse Rat
A19037 [KO Validated] Cyclin B1 Rabbit mAb WB Human Mouse
A16038 Cyclin B1 Rabbit pAb WB IHC IF IP Human Mouse Rat
A3351 CCNB2 Rabbit pAb WB IHC Human Mouse Rat
A19038 [KO Validated] Cyclin D1 Rabbit mAb WB IHC IF Human Mouse Rat
A11310 Cyclin D1 Rabbit pAb WB IP Human Mouse Rat
A1773 Cyclin D2 Rabbit pAb WB IHC IF Human Mouse Rat
A0746 [KO Validated] CCND3 Rabbit pAb WB Human Mouse
A3989 Cyclin D3/CCND3 Rabbit mAb WB Human Mouse Rat
A14225 CCNE1 Rabbit pAb WB Human Mouse Rat
A9305 Cyclin E2 Rabbit mAb WB Human
A4076 Cyclin H Rabbit mAb WB IHC IF Human Mouse
A0995 CCNH Rabbit pAb WB IP Human
p53 A19585 [KO Validated] p53 Rabbit mAb WB Human
A5761 p53 Rabbit pAb WB IHC IP ChIP Human Mouse Rat
A0263 p53 Rabbit pAb WB IHC IF ChIP Human Rat
A11232 [KO Validated] p53 Rabbit pAb WB IHC IF Human Mouse Rat
AP0985 Phospho-p53-S9 Rabbit mAb WB Human Mouse
AP0987 Phospho-p53-S376 Rabbit mAb WB Human Rat
AP0984 Phospho-p53-S33 Rabbit mAb WB Human
AP0986 Phospho-p53-T55 Rabbit mAb WB Human
AP0083 Phospho-p53-S15 Rabbit pAb WB IF IP Human Mouse Rat
AP0762 Phospho-p53-S33 Rabbit pAb WB IHC IP Human Mouse Rat
CKI A19094 [KO Validated] p21 Rabbit mAb WB IHC Human
A2691 [KO Validated] P21 Rabbit pAb WB IHC Human Mouse Rat
A1483 p21 Rabbit pAb WB IF Human Mouse Rat
A19095 [KO Validated] p27 KIP 1 Rabbit mAb WB IHC Human Mouse Rat
A0290 CDKN1B Rabbit pAb WB IHC IF Human Mouse Rat
A5685 CDKN2B Rabbit pAb WB Human
A11651 Rabbit mAb WB IHC IF Human
A0262 CDKN2A / p16INK4a Rabbit pAb WB IHC IF Human Mouse Rat
A6843 p57 Kip2 Rabbit mAb WB Human Mouse Rat
A8751 CDKN2C Rabbit mAb WB IF Human Mouse Rat

 

DNA Damage Repair Proteins
Target Name Cat.No. Product Name Applications Reactivity
PARP A19596 [KO Validated] PARP Rabbit mAb WB IHC Human Mouse Rat
A19612 Rabbit mAb WB Human Mouse
A0942 [KO Validated] PARP1 Rabbit pAb WB IHC IF IP ChIP Human Mouse Rat
Ape1 A11238 APE1 Rabbit mAb WB IHC Human Mouse Rat
A2587 [KO Validated] APEX1 Rabbit pAb WB IF IP Human
XRCC1 A4135 XRCC1 Rabbit mAb WB Human Mouse Rat
A0442 XRCC1 Rabbit pAb WB IF Human Mouse
PCNA A12427 PCNA Rabbit mAb WB IHC Human Mouse Rat
A0264 PCNA Rabbit pAb WB IHC IF Human Mouse Rat
FEN-1 A8999 FEN1 Rabbit mAb WB Human Mouse
A1175 FEN1 Rabbit pAb WB IHC IF IP Human Mouse
XPA A1626 [KO Validated] XPA Rabbit pAb WB IF Human Mouse
XPB A1714 ERCC3 Rabbit pAb WB IHC Human Mouse
XPC A8354 XPC Rabbit pAb WB IHC IP Human
XPD A14563 ERCC2 Rabbit pAb WB IF Human Mouse Rat
XPF A8119 ERCC4 Rabbit pAb WB IP Human Mouse Rat
DDB A5022 DDB1 Rabbit mAb WB Human Mouse Rat
A2896 DDB1 Rabbit pAb WB IHC IF Human Mouse Rat
A11615 DDB2 Rabbit mAb WB Human Mouse
A1848 DDB2 Rabbit pAb WB IF Human Mouse Rat
ERCC1 A5291 ERCC1 Rabbit pAb WB IF Human Mouse
MSH2 A8740 MSH2 Rabbit mAb WB Human Mouse Rat
A1121 MSH2 Rabbit pAb WB IP Human Mouse Rat
MSH3 A5681 MSH3 Rabbit pAb WB Human
MLH1 A4858 MLH1 Rabbit mAb WB Human Mouse
MLH3 A7796 MLH3 Rabbit pAb WB IF Human
PMS1 A2183 PMS1 Rabbit pAb WB Human
PMS2 A4577 PMS2 Rabbit mAb WB Human
BRCA2 A2435 BRCA2 Rabbit pAb WB IF Human Rat
FANCD2 A19692 FANCD2 Rabbit mAb WB Human Mouse Rat
CtIP A10201 RBBP8 Rabbit pAb WB Human Mouse Rat
Rad51 A6268 RAD51 Rabbit pAb WB Human Mouse Rat
A2829 Rad51 Rabbit mAb WB Human Mouse Rat
Rad52 A5186 RAD52 Rabbit mAb WB Human
XLF A19957 [KO Validated] NHEJ1 Rabbit pAb WB IHC IF Human Mouse Rat

 

References

Bernstein, C., Prasad, A.R., Nfonsam, V., and Bernstein, H. (May 22nd 2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Clark Chen, IntechOpen, DOI: 10.5772/53919. Available from: https://www.intechopen.com/chapters/43929.

BRCA gene Mutations: Cancer risk and genetic testing fact sheet. National Cancer Institute. (2020). https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#r2.

Herceg, Z., and Wang, Z.-Q. (2001). Functions of poly(adp-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 477(1-2), 97–110. https://doi.org/10.1016/s0027-5107(01)00111-7.

Hoeijmakers, J. H. J. (2009). DNA Damage, Aging, and Cancer. The New England Journal of Medicine, 316(15). https://doi.org/10.1056/nejmra0804615.

Konecny, G. E., and Kristeleit, R. S. (2016). PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: Current practice and future directions. British Journal of Cancer, 115(10), 1157–1173. https://doi.org/10.1038/bjc.2016.311.

Kunkel, T. A., & Erie, D. A. (2005). DNA mismatch repair. Annual Review of Biochemistry, 74(1), 681–710. https://doi.org/10.1146/annurev.biochem.74.082803.133243

McCabe, N., Turner, N. C., Lord, C. J., Kluzek, K., Białkowska, A., Swift, S., Giavara, S., O'Connor, M. J., Tutt, A. N., Zdzienicka, M. Z., Smith, G. C. M., & Ashworth, A. (2006). Deficiency in the repair of dna damage by homologous recombination and sensitivity to poly(adp-ribose) polymerase inhibition. Cancer Research, 66(16), 8109–8115. https://doi.org/10.1158/0008-5472.can-06-0140.

Tags: Antibodies, Proteins, DNA Damage & Repair, Molecular Biology

Eva Volckova

Eva Volckova

Eva Volckova attends Mount Holyoke college, where she’s studying biology and chemistry.