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DNA Structure, Damage, and Repair

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Related Resources: Brochures | Application Notes
Because chromosomal DNA is the template for the generation of all RNA and protein expressed in a cell, the integrity of the DNA sequence needs to be maintained throughout a cells life. If damage occurs and it is not properly repaired, mutations will collect and potentially result in the development of disease. Damage to DNA can occur through a variety of mechanisms such as environmental exposure to mutagenic chemicals or damaging radiation. Additionally, standard cellular functions such as normal cellular metabolism, the generation of free radicals, hydrolysis of bases (deamination, depurination, depyridination) and DNA replication errors can all result in DNA damage.
To maintain the stability of their genome, cells have developed multi-component damage detection and repair systems to address single strand damage as well as double strand breaks. Examples of single strand damage repair systems include nucleotide excision repair (NER), base excision repair (BER), and mismatch repair. Double stranded breaks are addressed using one of the double strand break repair mechanisms (DSBs). These mechanisms are known as non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination.

At sites of DNA damage histone H2A.X is recruited to the site and becomes phosphorylated at serine 139. This histone also known as gamma H2A.X serves as a binding site for MDC1 which helps recruited DNA repair proteins

In dividing cells, cell cycle check points are activated in response to DNA damage. These check points result in a pause to cell division and allow the repair mechanisms to function. If these detection and repair systems fail, cells can become senescent, apoptotic, or undergo autophagy to prevent the cells from proliferating. If these ‘back-up systems’ fail these aberrant cells survive and continue to divide and result in the development of diseases such as cancer. In some cases the repair mechanisms are unable to detect the error. When errors in DNA methylation occur such as the spontaneous deamination of 5-methylcytosine, the loss of the amine group yields a thymine base. This change is not detected as an unnatural base. The resulting substitution is retained in DNA replication, creating a C→T point mutation.

Merck offers a wide variety of antibodies for laboratories studying the mechanisms by which cells respond to DNA damage and initiate repair. The tables provide just a few examples of the targets for studying DNA damage and repair and its relation to aging, cellular degeneration, cancer, and death. Don’t see your specific target? Use our antibody search tool to find the exact antibody you need.

Featured Antibody: Anti-XRCC1
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Staining of A431 cells using Anti-XRCC1 (Cat. No. ABC738, green). Microtubules are shown in red. This antibody positively stains the nucleus.

Telomere Maintenance

Located at the ends of eukaryotic chromosomes, telomeres consist of thousands of DNA repeats. Telomeres protect chromosome ends, limiting fusion, rearrangement and translocation. As cells divide, the telomere ends of chromosomes get shorter because at each cell division DNA polymerase cannot synthesize the 5’ end of the lagging strand. Eventually, the telomerase, the enzymatic ribonucleoprotein that adds telomeric repeats using its RNA component as a template, gets silenced. This resulting in telomeres are too short for cells to divide. Shortened telomeres are associated with aging cells that are senescent.

Telomeres at the ends of chromosomes, like all other sections of DNA, are prone to DNA damage, including double-strand breaks (DSBs). And unlike the rest of the chromosome, telomere DSBs aren’t fixed by the DNA repair pathway, as this would frequently lead to fused chromosomes and genomic instability.

Featured Antibody: Anti-Zscan4
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Staining of mouse R1 Embyonic Stem cells using Anti-Zscan4 (Cat. No. AB4340, red). Nuclei are stained with DAPI (blue).

Telomere and Telomerase Antibodies

Related Products:
Telomerase Assays