• enzyme
  • DNA-(apurinic or apyrimidinic site) lyase is an enzyme that in humans is encoded by the APEX1 gene. (wikipedia.org)
  • In the 1970s, this class of enzyme was found to repair at apurinic or apyrimidinic DNA sites in E. coli and in mammalian cells. (wikipedia.org)
  • Since DNA AP lyase is a class of structures who have numerous target genes that encode for different variations of the enzyme, there is no one single enzyme structure that can be used as an example that encompasses all versions of the enzyme. (wikipedia.org)
  • Furthermore, the catalytic mechanism of AP lyases, the β-elimination reaction, proceeds through an imine enzyme-DNA intermediate. (wikipedia.org)
  • Phage-T4 UV endonucleases also catalyze the reaction of the δ-reaction, nicking C5'-O-P bond at AP sites, although this reaction is slow and the enzyme should still be classified as AP lyase. (wikipedia.org)
  • Poly (ADP-ribose) polymerase 1 (PARP1) is an ADP-ribosylating enzyme essential for initiating various forms of DNA repair. (mdpi.com)
  • Inhibiting its enzyme activity with small molecules thus achieves synthetic lethality by preventing unwanted DNA repair in the treatment of cancers. (mdpi.com)
  • Besides presenting current findings on how each process is individually controlled by PARP1, we shall discuss how transcription and DNA repair are so intricately linked that disturbance by PARP1 enzymatic inhibition, enzyme hyperactivation in diseases, and viral replication can favor one function while suppressing the other. (mdpi.com)
  • Poly (ADP-ribose) polymerase 1 (PARP1) is well known as an ADP-ribosylating enzyme, which becomes activated upon binding to DNA single-strand and double-strand breaks (ssDB and dsDB respectively) [ 1 , 2 , 3 , 4 , 5 , 6 ]. (mdpi.com)
  • As an enzyme, PARP1 acts on chromatin remodeling complexes to control DNA accessibility for RNA polymerase [ 18 , 19 , 20 , 21 , 22 ]. (mdpi.com)
  • DNA repair enzyme that incises DNA at 8-oxoG residues. (uniprot.org)
  • The primary function of the MUTYH gene is the production of the glycosylase enzyme which catalyzes the removal of 8-0x0G (also 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-Oxoguanine), the result of base pair transversion. (wikipedia.org)
  • The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. (wikipedia.org)
  • The bi-functional hOGG1 enzyme is responsible for the excision of 8-oxoguanine (8-oxoG) with combined glycosylase/lyase activity. (rsc.org)
  • Conventional methods for DNA glycosylase ( e.g. hOGG1 and hAAG) assay include radioactive labeling, enzyme-linked immunosorbent assay, high-performance liquid chromatography, 13 magnetic nanoparticle-based separation techniques, 21 gold nanoparticle-based colorimetric assay, 22,23 and electrochemiluminescent 24 and fluorescent methods. (rsc.org)
  • This structure revealed that the enzyme flips the damaged base out of the double helix into an active site pocket in order to excise it. (wikipedia.org)
  • DNA ligase 1 is an enzyme that in humans is encoded by the LIG1 gene. (wikipedia.org)
  • Previously it had been known that DNA replication occurred through the breakage of the double DNA strand, but the mechanism of action and enzyme responsible for ligating the strands back together was unknown. (wikipedia.org)
  • The LIG1 gene encodes a, 120kDa enzyme, 919 residues long, known as DNA ligase I. The DNA ligase I polypeptide contains an N-terminal replication factory-targeting sequence (RFTS), followed by a nuclear localization sequence (NLS), and three functional domains. (wikipedia.org)
  • In order to ligate these fragments together, the ligase progresses through three steps: Addition of an adenosine monophosphate (AMP) group to the enzyme, referred to as adenylylation, Adenosine monophosphate transfer to the DNA and Nick sealing, or phosphodiester bond formation. (wikipedia.org)
  • lesion
  • The nucleosome presents a particular challenge to BER enzymes: the rate and efficiency of repair at a particular lesion site are expected to depend on the relative rotational and translational position of the lesion site on the histone core. (jbsdonline.com)
  • Here, we examine the rate and efficiency of the removal of 8-oxo-7,8-dihydroguanine (8-oxoG), the predominant oxidative lesion in DNA (Michaels & Miller, 1992), by the glycosylase hOGG1 as a function of position within the nucleosome. (jbsdonline.com)
  • In particular, the 8‐oxoguanine (GO) lesion is one of the most stable products of oxidative DNA damage ( Dizdaroglu, 1985 ). (embopress.org)
  • gene
  • Functional dissection of siRNA sequence by systematic DNA substitution: modified siRNA with a DNA seed arm is a powerful tool for mammalian gene silencing with significantly reduced off-target effect. (abnova.com)
  • There is an helix-hairpin-helix and pseudo helix-hairpin-helix contained within the N-terminal, in addition to and iron cluster motif The BER (base excision repair) employed by the gene is the result of a collaborative effort by both MUTYH and OGG1. (wikipedia.org)
  • strand
  • The nick sealing of the strands is accomplished by the formation of LIG1 (DNA ligase 1) and/or LIG3/ XRCCI complex that attach to processed end of the corrected strands and reinstate the original conformation of the strand. (wikipedia.org)
  • Both the polymerases repair the DNA by employing the strand displacement synthesis mechanism. (wikipedia.org)
  • Other notable interactions include MUTYH and Replication protein A is a single strand binding protein that prevents the annealing of DNA during replication, it also plays a role as an activator for damage repair on DNA. (wikipedia.org)
  • Both mechanisms form a single-strand break, which is then repaired by either short-patch or long-patch base excision repair. (wikipedia.org)
  • To be specific, HMGA2-high cancers display an abnormally strong response to double strand breaks in DNA caused by radiation therapy and some forms of chemotherapy. (wikipedia.org)
  • In order for ligation to occur, a DNA strand break must have a hydroxyl on its 3' end and a phosphate on its 5' end. (wikipedia.org)
  • If the Okazaki fragments are not properly ligated together, the unligated DNA (containing a 'nick') could easily degrade to a double strand break, a phenomenon known to cause genetic mutations. (wikipedia.org)
  • zinc
  • The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. (wikipedia.org)
  • replication
  • AP sites are pre-mutagenic lesions that can prevent normal DNA replication. (wikipedia.org)
  • AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. (abnova.com)
  • If left unrepaired, AP sites can lead to mutation during semiconservative replication. (wikipedia.org)
  • BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. (wikipedia.org)
  • 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. (wikipedia.org)
  • DNA ligases are important tools for DNA replication and repair in living organisms. (wikipedia.org)
  • Of the known eukaryotic DNA ligases, DNA ligase I is the only ligase involved in DNA replication making it the most studied of the ligases. (wikipedia.org)
  • The N-terminus of the protein contains a replication factory-targeting sequence that is used to recruit it to sites of DNA replication known as replication factories. (wikipedia.org)
  • Together, the N-terminal serines are substrates of the CDK and CKII, which appear to play an important regulatory role DNA ligase I recruitment to the replication factory during S-phase of the cell cycle. (wikipedia.org)
  • LIG1 encodes DNA ligase I, which functions in DNA replication and the base excision repair process. (wikipedia.org)
  • DNA ligase 1 utilizes adenosine triphosphate (ATP) to catalyze the energetically favorable ligation events in both DNA replication and repair. (wikipedia.org)
  • During the synthesis phase (S-phase) of the eukaryotic cell cycle, DNA replication occurs. (wikipedia.org)
  • transcriptional
  • Besides DNA repair, the importance of PARP1 as a transcriptional regulator is also well established. (mdpi.com)
  • In this review, we will summarize the roles of PARP1 in DNA repair and transcriptional regulation. (mdpi.com)
  • This protein contains structural DNA-binding domains and may act as a transcriptional regulating factor. (wikipedia.org)
  • mechanism
  • Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. (wikipedia.org)
  • There are four types of AP endonucleases that have been classified according to their mechanism and site of incision. (wikipedia.org)
  • Class II AP endonucleases incise DNA 5' to AP sites by a hydrolytic mechanism, leaving a 3'-hydroxyl and a 5'-deoxyribose phosphate residue. (wikipedia.org)
  • Artificial addition of HMGA2 to some forms of cancer unresponsive to DNA damage cause them to respond to the treatment instead, although the mechanism by which this phenomenon occurs is also not understood. (wikipedia.org)
  • In biochemistry and genetics, base excision repair (BER) is a cellular mechanism that repairs damaged DNA throughout the cell cycle. (wikipedia.org)
  • In the 1960s Lehman laboratories investigated this mystery, discovering DNA ligase and its mechanism of action in 1967. (wikipedia.org)
  • mutagenic
  • The critical role of PARP1 in DNA repair is reflected by its frequent upregulation in cancer [ 8 , 9 ], as well as the hypersensitivity of PARP1 null animals towards the mutagenic effects of DNA damaging agents [ 10 ]. (mdpi.com)
  • Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. (uniprot.org)
  • These gap sites are mutagenic in nature and require constant and immediate emendation and this is achieved by the active involvement of protein complexes that repair the AP gap site via short and long patch repair pathways. (wikipedia.org)
  • genomic
  • In eukaryotic cells, short stretches (146 base pairs) of genomic DNA are wrapped around octameric clusters of histone proteins, forming macromolecular structures called nucleosomes (Eickbush & Moudrianakis, 1978). (jbsdonline.com)
  • Genomic_DNA. (genome.jp)
  • protein
  • HMGA2 contains three basic DNA-binding domains (AT-hooks) that cause the protein to bind to adenine-thymine (AT)-rich regions of nuclear DNA. (wikipedia.org)
  • HMGA2 does not directly promote or inhibit the transcription of any genes, but alters the structure of DNA and promotes the assembly of protein complexes that do regulate the transcription of genes. (wikipedia.org)
  • ligase
  • DNA ligase I is found in eukaryotes and therefore is in the family of ATP-dependent DNA ligases. (wikipedia.org)
  • Activation and recruitment of DNA Ligase I seem to be associated with posttranslational modifications. (wikipedia.org)
  • Eukaryotic DNA ligase 1 catalyzes a reaction that is chemically universal to all ligases. (wikipedia.org)
  • During adenylylation, there is a nucleophilic attack on the alpha phosphate of ATP from a catalytic lysine resulting in the production of inorganic pyrophosphate (PPi) and a covalently bound lysine-AMP intermediate in the active site of DNA ligase 1. (wikipedia.org)
  • During the AMP transfer step, the DNA ligase becomes associated with the DNA, locates a nick and catalyzes a reaction at the 5' phosphate site of the DNA nick. (wikipedia.org)
  • functions
  • Through the motif-PARP1 interaction, we will also discuss how transcription and DNA repair affect one another in normal cell functions and diseases states. (mdpi.com)
  • Nucleotide
  • Next, electrons from one of the oxygen atom in the phosphate group moves down, kicking off one of the other oxygen to create a free 5´ phosphate group on the AP site and a free 3´-OH on the normal nucleotide, both of which are stabilized by the Mg2+ ion. (wikipedia.org)
  • phosphate
  • The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. (uniprot.org)
  • The AP site is then further stabilized through hydrogen bonding of the phosphate group 5´ to the AP site with Asn174, Asn212, His309, and the Mg2+ ion while its orphan base partner is stabilized through hydrogen bonding with Met270. (wikipedia.org)
  • The phosphate group 3' to the AP site is stabilized through hydrogen bonding to Arg177. (wikipedia.org)
  • First, the Asp210 residue in the active site deprotonates a water molecule, which can then perform a nucleophilic attack on the phosphate group located 5´ to the AP site. (wikipedia.org)
  • An anionic oxygen on the 5' phosphate of the DNA nick serves as the nucleophile, attacking the alpha phosphate of the covalently bound AMP causing the AMP to be covalently bound intermediate (DNA-AMP intermediate). (wikipedia.org)
  • Specificity
  • 25 However, these methods suffer from some limitations, such as the involvement of costly labeling reagents, low specificity, tedious DNA fragmentation and expensive instrumentation, 13 long analysis time and complicated procedures, 21-23 and low detection sensitivity. (rsc.org)
  • lesions
  • It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. (wikipedia.org)