Types of dna damage

How can DNA be repaired? Damage to DNA that occurs naturally can result from metabolic or hydrolytic processes. What is the best ancestry kit? Metabolism releases compounds that damage DNA including reactive oxygen species, reactive nitrogen species, reactive carbonyl species, lipid peroxidation products and alkylating agents, among others, while hydrolysis cleaves chemical bonds in DNA. Since the sources of DNA damage can be roughly divided into two main groups, endogenous damage and exogenous damage.

DNA may be modified in a variety of ways, which can ultimately lead to mutations and genomic instability.

This could result in the development of a variety of cancers including colon, breast, and prostate. Here we discuss the various types of damage to DNA , including oxidative damage , hydrolytic damage , DNA strand breaks, and others. Oxygen and light are major causes of DNA damage. DNA damage can be subdivided into two types : (1) endogenous damage caused by reactive oxygen species (ROS) that are derived from metabolic byproducts and (2) exogenous damage caused by radiation (UV, X-ray, gamma), hydrolysis, plant toxins, and viruses.

Damage to cellular DNA is involved in mutagenesis and the development of cancer. The DNA in a human cell undergoes several thousand to a million damaging events per day, generated by both external (exogenous) and internal metabolic (endogenous) processes. Changes to the cellular genome can generate errors in the transcription of DNA and ensuing translation into proteins necessary for signaling and cellular function.

Genomic mutations can also be carried over into daughter generations of cells if the mutation is not repaired prior to mitosis. Once cells lose their ability to effectively repair damaged DNA , there are three possible responses (see Figure 1).

The cell may become senescent, i. Sufficient DNA damage may trigger an apoptotic signaling. See full list on sigmaaldrich. For many years, exogenous sources of damage have been thought to be the primary cause of DNA mutations leading to cancer. However, Jackson and Loeb proposed that endogenous sources of DNA damage also contribute significantly to mutations that lead to malignancy. Both environmental and cellular sources can result in similar types of DNA damage.

DNA can be attacked by physical and chemical mutagens. UV radiation produces covalent bonds that crosslink adjacent pyrimidine (cytosine and thymine) bases in the DNA strand. Ionizing radiation (X-rays) initiates DNA mutations by generating free radicals within the cell that create reactive oxygen species (ROS) and result in single-strand and double-strand breaks in the double helix. While the cell is able to evolve into either an apoptotic or senescent state, these actions are performed as a last resort. For each type of DNA damage, the cell has evolved a specific method of repairing the damage or eliminating the damaging compound.

The reaction is not a catalytic (enzymatic) reaction but is stoichiometric (chemical), consuming one molecule of MGMT for each adduct removed. Cells that have been engineered to overexpress MGMT are more resistant to cancer, likely because they are able to negate a larger amount of alkylating damage. A recent study by Niture, et al. DNA polymerases such as polymerase-δ contain proofreading activities and are primarily involved in replication error repair. Base excision repair (BER) involves multiple enzymes to excise and replace a single damaged nucleotide base.

When an error is detec. The base modifications primarily repaired by BER enzymes are those damaged by endogenous oxidation and hydrolysis. A DNA glycosylase cleaves the bond between the nucleotide base and ribose, leaving the ribose phosphate chain of the DNA intact but resulting in an apurinic or apyrimidinic (AP) site.

Oxoguanine DNA glycosylase I (Ogg1) removes 8-dihydro-8-oxoguanine (8-oxoG), one of the base mutations generated by reactive oxygen species. Polymorphism in the human OGGgene is associated with the risk of various cancers such as lung and prostate cancer. N-Methylpurine DNA glycosylase (MPG) is able to remove a variety of modified purine bases. The AP sites in the DNA that result from the action of BER enzymes, as. Double-strand breaks in DNA can result in loss and rearrangement of genomic sequences.

These breaks are repaired by either nonhomologous end-joining (NHEJ) or by homologous recombination (HR), also called recombinational repair or template–assisted repair. This mechanism requires the presence of an identical or nearly identical sequence linked to the damaged DNA region via the centromere for use as a repair template. Non-homologous end-joining (NHEJ) is used at other points of the cell cycle when sister chromatids are not available for use as HR templates. While DNA damage is a key factor in the development and evolution of cancer cells, continued damage is used as part of clinical treatments for cancer, forcing malignant cells into apoptosis or senescence.

Many chemotheraputic drugs such as bleomycin, mitomycin, and cisplatin, are effective because they cause further DNA damage in cancer cells that replicate at a faster rate than surrounding tissue. In order to block this survival mechanism within cancer cells, clinical trials are now being performed using inhibitors to specific DNA repair enzymes, including MGMT, PARP, and DNA -PK. Discover More about your Paternal Ancestry and Connect with Your Y- DNA Relatives.

Note that many types of DNA damage are generated spontaneously, in some cases at very high frequency. Thus defects in DNA repair systems are likely to cause problems even in the absence of additional damage caused by environmental factors. An overview of DNA damage , DNA sensing, DNA repair, and mutagenesis was considered essential to begin a book about dietary factors that may alter how the cell deals with DNA damage.

Thus, this review was written to provide the necessary background information for the reader to understand the rest of the book. Successful DNA replication requires that the two purine bases, adenine (A) and guanine (G), pair with their pyrimidine counterparts, thymine (T) and cytosine (C). Different types of damage , however, can prevent correct base pairing, among them spontaneous mutations, replication errors, and chemical modification.

NA damage is an alteration in the chemical structure of DNA , such as a break in a strand of DNA , a base missing from the backbone of DNA , or a chemically cha.