Which Enzymes Are Involved In Base Excision Repair?

DNA repair is a complex process that involves several multienzyme, multistep processes to maintain the cellular genome against genotoxic insults. One of these processes is base excision repair (BER), which corrects forms of oxidative, deamination, alkylation, and abasic single-base damage that appear insignificant to the helix. BER is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or cytosine (Cyt).

The repair of free bases is catalyzed by a class of enzymes called DNA glycosylases. Each known DNA glycosylase more or less uniquely identifies and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or cytosine. The BER pathway, comprising several enzymes including a DNA glycosylase, APE1, DNA polymerase, and DNA ligase, along with several accessory enzymes, is involved in active DNA demethylation, a multistep pathway that erases the epigenetic mark 5-methylcytosine (5mC) and derivatives.

The main emphasis is on the role of BER in active DNA demethylation, a multistep pathway that erases the epigenetic mark 5-methylcytosine (5mC) and derivatives. The repair of base lesions generally requires five enzymatic activities: glycosylase, endonuclease, lyase, polymerase, and ligase. Protein cofactors and mechanisms for coordinating the repair of base lesions are also discussed.

In summary, DNA repair is a multienzyme process that includes nucleotide excision repair, base excision repair, and mismatch repair. The BER pathway, which includes several enzymes, plays a crucial role in maintaining the integrity of the cellular genome against genotoxic insults.

Which polymerase is used in base excision repair?

Abstract. There are five well-characterized nuclear DNA polymerases in eukaryotes (DNA polymerases alpha, beta, delta, epsilon and zeta) and this short review summarizes our current knowledge concerning the participation of each in DNA-repair. The three major DNA excision-repair pathways involve a DNA synthesis step that replaces altered bases or nucleotides removed during repair. Base excision-repair removes many modified bases and abasic sites, and in mammalian cells this mainly involves DNA polymerase beta. An alternative means for completion of base excision-repair, involving DNA polymerases delta or epsilon, may also operate and be even more important in yeast. Nucleotide excision-repair uses DNA polymerases delta or epsilon to resynthesize the bases removed during repair of pyrimidine dimers and other bulky adducts in DNA. Similarly, mismatch-repair of replication errors appears to involve DNA polymerases delta or epsilon. DNA polymerase alpha is required for semi-conservative replication of DNA but not for repair of DNA. A more recently discovered enzyme, DNA polymerase zeta, appears to be involved in the bypass of damage, without excision, and occurs during DNA replication of a damaged template.

(Eukaryotic error prone DNA polymerases: suggested roles in replication, repair and mutagenesis).

Krutiakov VM. Krutiakov VM. Mol Biol (Mosk). 2006 Jan-Feb;40:3-11. Mol Biol (Mosk). 2006. PMID: 16523685 Review. Russian.

Is DNA ligase used in nucleotide excision repair?

DNA Ligases I and III Support Nucleotide Excision Repair in DT40 Cells with Similar Efficiency. Photochem Photobiol.

Which of the following enzymes are involved in specific excision repair?

Proteins involved in base excision repairDNA glycosylases. AP endonucleases. End processing enzymes. DNA polymerases. Flap endonuclease. DNA ligase.

Base excision repair ( BER ) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch (where a single nucleotide is replaced) or long-patch BER (where 2–10 new nucleotides are synthesized).

Single bases in DNA can be chemically damaged by a variety of mechanisms, the most common ones being deamination, oxidation, and alkylation. These modifications can affect the ability of the base to hydrogen-bond, resulting in incorrect base-pairing, and, as a consequence, mutations in the DNA. For example, incorporation of adenine across from 8-oxoguanine (right) during DNA replication causes a G:C base pair to be mutated to T:A. Other examples of base lesions repaired by BER include:

• Oxidized bases : 8-oxoguanine, 2, 6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG, FapyA)
• Alkylated bases : 3-methyladenine, 7-methylguanosine
• Deaminated bases : hypoxanthine formed from deamination of adenine. Xanthine formed from deamination of guanine. ( Thymidine products following deamination of 5-methylcytosine are more difficult to recognize, but can be repaired by mismatch-specific glycosylases)
• Uracil inappropriately incorporated in DNA or formed by deamination of cytosine

Which enzyme is responsible for excising damaged DNA?

Uracil-containing DNA repair is a form of base-excision repair, where single damaged bases are recognized and removed from the DNA molecule. Uracil can arise in DNA through two mechanisms: uracil is incorporated in place of thymine during DNA synthesis, or uracil is formed by the deamination of cytosine. The second mechanism is of greater biological significance as it alters the normal pattern of complementary base pairing and represents a mutagenic event. DNA glycosylase catalyzes the excision of uracil in DNA, cleaving the bond linking the base to the deoxyribose of the DNA backbone. This reaction yields free uracil and an apyrimidinic site, a sugar with no base attached. DNA glycosylases also recognize and remove other abnormal bases, including hypoxanthine formed by the deamination of adenine, pyrimidine dimers, alkylated purines other than O 6 -alkylguanine, and bases damaged by oxidation or ionizing radiation. The result of DNA glycosylase action is the formation of an apyridiminic or apurinic site (AP site), which is formed due to the spontaneous loss of purine bases. These sites are repaired by AP endonuclease, which cleaves adjacent to the AP site, and the remaining deoxyribose moiety is removed.

What are the enzymes in end repair?

The End Repair Enzyme Mix contains an optimized mixture of T4 DNA Polymerase and Klenow Fragment to achieve highly effective blunting of fragmented DNA, and T4 Polynucleotide Kinase for efficient phosphorylation of DNA ends.

What are the 4 major enzymes?

The four main enzymes involved in DNA replication are DNA helicase, RNA primase, DNA polymerase, and DNA ligase.

What are the enzymes in base excision repair?

Apurinic/apyrimidinic endonuclease-1 (APE1) is one of the key enzymes in the base excision repair (BER) pathway; its function is to cleave the apurinic/apyrimidinic sites (Parsons et al., 2004; Srivastava et al., 1998).

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What are the two functions for the enzyme APE1 in the base excision repair process?

APE1 is a multifunctional protein that plays a dual role in DNA repair and transcriptional regulation. It is the main apurinic/apyrimidinic endonuclease in eukaryotic cells, playing a central role in the DNA base excision repair pathway of all DNA lesions, including single-strand breaks. APE1 also has cotranscriptional activity by modulating genes expression directly regulated by either ubiquitous (AP-1, Egr-1, NF-κB, p53, and HIF) and tissue specific (PEBP-2, Pax-5 and −8, and TTF-1) transcription factors. It also controls the intracellular redox state by inhibiting reactive oxygen species (ROS) production.

APE1’s redox function is found only in mammals and not in other vertebrates, as demonstrated by the lack of redox function in the Zebrafish APE1 (zAPE). The acquisition of the redox function in APE1 proteins is discussed in a recent publication. The two major functions of APE1, redox and repair, are completely independent in their actions. Mutations of the Cys at position 65 (C65) abolish the redox function but do not affect the repair function, while mutations of various amino acids required for DNA repair activity do not affect the redox function.

While the DNA repair active site of APE1 has been clearly delineated, the redox domain is much less defined. The only Cys residue required for full redox function is C65, which is buried within the APE1 protein. Recently, Georgiadis mutated in the zAPE1 a Thr (T58) to a Cys located at the same position of the Cys in the mammalian APE1, resulting in the acquisition of redox activity of the mutated protein.

What does AP Lyase do?

DNA (Apurinic or Apyrimidinic Site) Lyase is an enzyme that cleaves the DNA backbone at the site where a base has been removed, creating a single-strand break with a 3′-hydroxyl and 5′-phosphate termini.

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What does base excision repair use?

BER involves removing the base from the deoxyribose-phosphate chain by a specific glycosylase, endonuclease action, DNA polymerase Beta, and either DNA ligase I or DNA ligase III/XRCC1 complex.

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What are the repair enzymes?

Repair enzymes recognize and remove DNA adducts, correct the DNA sequence, and rejoin strand breaks.

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