• genetics
  • In genetics, Flp-FRT recombination is a site-directed recombination technology, increasingly used to manipulate an organism's DNA under controlled conditions in vivo. (wikipedia.org)
  • Genome
  • A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers. (biomedsearch.com)
  • This analysis validated the approach of whole cancer genome sequencing in identifying somatic mutations and the importance of parallel sequencing of normal and tumor cell genomes. (wikipedia.org)
  • Ligases are versatile and ubiquitous enzymes that join the 3' hydroxyl and 5' phosphate ends to form a phosphodiester bond, making them essential in nicked DNA repair, and ultimately genome fidelity. (wikipedia.org)
  • DNA mismatch repair (MMR) is an important DNA repair system that helps maintain genome plasticity by correcting mismatches, or non Watson-Crick base pairs in the a DNA duplex. (wikipedia.org)
  • Transposition is a precise process in which a defined DNA segment is excised from one DNA molecule and moved to another site in the same or different DNA molecule or genome. (wikipedia.org)
  • The elevation of DNA-PKcs is thought to reflect the induction of a compensatory DNA repair capability, due to the genome instability in these cancers. (wikipedia.org)
  • Φ29 is a bacteriophage of Bacillus subtilis with a sequenced, linear, 19,285 base pair DNA genome. (wikipedia.org)
  • cleavage
  • A general role of the DNA glycosylase Nth1 in the abasic sites cleavage step of base excision repair in Schizosaccharomyces pombe. (biomedsearch.com)
  • Analysis of the AP site cleavage in whole cell extracts of wild-type and mutant strains showed that the AP lyase activity of Nth1 represents the major AP site incision activity in vitro. (biomedsearch.com)
  • 397 1: 161-78 Preferred sequences within a defined cleavage window specify DNA 3' end-directed cleavages by retroviral RNases H. Schultz SJ, Zhang M, Champoux JJ The Journal of Biological Chemistry. (wikipedia.org)
  • The nucleophilic properties of the tyrosine attack and bind to the 3'-phosphate at the point of DNA cleavage. (wikipedia.org)
  • cancers
  • BRCA1 breast cancers displayed a mutational signature consistent with that caused by lack of HR DNA repair in both ER-positive and ER-negative cases. (biomedsearch.com)
  • A number of recently devised methods can assess the DNA methylation status in cancers versus normal tissues. (wikipedia.org)
  • DNA-PKcs expression was reduced by 23% to 57% in six cancers as indicated in the table. (wikipedia.org)
  • It is not clear what causes reduced expression of DNA-PKcs in cancers. (wikipedia.org)
  • Elevated DNA-PKcs expression is found in a large fraction (40% to 90%) of some cancers (the remaining fraction of cancers often has reduced or absent expression of DNA-PKcs). (wikipedia.org)
  • As indicated in a table listing 12 types of cancer reported in 20 publications, the fraction of cancers with over-expression of DNA-PKcs is often associated with an advanced stage of the cancer and shorter survival time for the patient. (wikipedia.org)
  • However, the table also indicates that for some cancers, the fraction of cancers with reduced or absent DNA-PKcs is also associated with advanced stage and poor patient survival. (wikipedia.org)
  • excision
  • A mutant lacking the DNA glycosylase/AP lyase Nth1 is very sensitive to the alkylating agent methyl methanesulfonate (MMS), suggesting a role for Nth1 in base excision repair (BER) of alkylation damage. (biomedsearch.com)
  • Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. (wikipedia.org)
  • In addition to their role in base excision repair, DNA glycosylase enzymes have been implicated in the repression of gene silencing in A. thaliana, N. tabacum and other plants by active demethylation. (wikipedia.org)
  • Nucleotide excision repair (NER) is a major pathway for repairing a variety of bulky DNA damages including those introduced by UV irradiation. (wikipedia.org)
  • Mouse models of nucleotide-excision-repair syndromes reveal a striking correlation between the degree to which specific DNA repair pathways are compromised and the severity of accelerated aging, strongly suggesting a causal relationship. (wikipedia.org)
  • deamination
  • Current evidence suggests that, in human cells, TDG and SMUG1 are the major enzymes responsible for the repair of the U:G mispairs caused by spontaneous cytosine deamination, whereas uracil arising in DNA through dU misincorporation is mainly dealt with by UNG. (wikipedia.org)
  • backbone
  • Each model predicts distinct sets of interactions between surface arginines and negatively charged phosphates in the DNA backbone. (mdpi.com)
  • This leads to a different DNA conformation, where a hydrogen bond forms in place of the missing piece of the DNA backbone in order to preserve the structure. (wikipedia.org)
  • At the end of the segment that DNA polymerase acts on, DNA ligase must repair the final segment of DNA backbone in order to complete the repair process. (wikipedia.org)
  • Pinch: UDG scans DNA for uracil by nonspecifically binding to the strand and creating a kink in the backbone, thereby positioning the selected base for detection. (wikipedia.org)
  • This compression of the DNA backbone, or "pinch," allows for close contact between UDG and base of interest. (wikipedia.org)
  • Mechanism
  • His interests are retroviruses and topoisomerases and his highest cited paper is DNA Topoisomerases: Structure, Function, and Mechanism at 222 times, according to Google Scholar. (wikipedia.org)
  • DNA Topoisomerases: Structure, Function, and Mechanism, Vol. 70:369-413 (Volume publication date July 2001). (wikipedia.org)
  • This family of recombinases performs its function via a type IB topoisomerase mechanism causing the recombination of two separate strands of DNA. (wikipedia.org)
  • In the 1960s Lehman laboratories investigated this mystery, discovering DNA ligase and its mechanism of action in 1967. (wikipedia.org)
  • ligase
  • One particular example of a ligase catalyzing nick closure is the E. coli NAD+ dependent DNA ligase. (wikipedia.org)
  • The ligase forms a DNA-adenylate complex, assisting recognition. (wikipedia.org)
  • With human DNA ligase, this forms a crystallized complex. (wikipedia.org)
  • The complex, which has a DNA-adenlyate intermediate, allows DNA Ligase I to institute a conformational change in the DNA for the isolation and subsequent repair of the DNA nick. (wikipedia.org)
  • 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)
  • Adducts
  • DNA damage is any physical abnormality in the DNA, such as single and double strand breaks, 8-hydroxydeoxyguanosine residues and polycyclic aromatic hydrocarbon adducts. (wikipedia.org)
  • conformational change
  • Autophosphorylation of DNA-PKcs appears to play a key role in NHEJ and is thought to induce a conformational change that allows end processing enzymes to access the ends of the double-strand break. (wikipedia.org)
  • Push: To fully assess the nucleotide identity, the intercalation loop penetrates, or pushes into, the DNA minor groove and induces a conformational change to flip the nucleotide out of the helix. (wikipedia.org)
  • sequences
  • The genomics era began in the 1990s, with the generation of DNA sequences of many organisms. (wikipedia.org)
  • The Sleeping Beauty transposon system is composed of a Sleeping Beauty (SB) transposase and a transposon that was designed in 1997 to insert specific sequences of DNA into genomes of vertebrate animals. (wikipedia.org)
  • eukaryotes
  • The human gene is well researched and orthologs exist ubiquitously among prokaryotes and eukaryotes and even in some DNA viruses. (wikipedia.org)
  • Sequence
  • Sequence analysis of the URA3 mutants revealed approximately 48% frameshifts, approximately 44% base substitutions and approximately 8% complex events. (biomedsearch.com)
  • As do all other Tc1/mariner-type transposases, SB transposase inserts a transposon into a TA dinucleotide base pair in a recipient DNA sequence. (wikipedia.org)
  • Alterations
  • DNA Alterations in Primary and Circulating Tumors, Non-Coding RNAs for Cancer Classification, Detection, and Monitoring, Identifying Pred. (utah.edu)
  • Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair. (wikipedia.org)
  • repair
  • Nicks are also thought to play a role in the DNA mismatch repair mechanisms that fix errors on both the leading and lagging daughter strands. (wikipedia.org)
  • On the lagging strand, nicks exist between Okazaki fragments and are easily recognizable by the DNA mismatch repair machinery prior to ligation. (wikipedia.org)
  • DNA-PKcs is required for the non-homologous end joining (NHEJ) pathway of DNA repair, which rejoins double-strand breaks. (wikipedia.org)
  • If DNA repair is deficient, DNA damage tends to accumulate. (wikipedia.org)
  • HMGA2 delays the release of DNA-PKcs from sites of double-strand breaks, interfering with DNA repair by non-homologous end joining and causing chromosomal aberrations. (wikipedia.org)
  • When cancer cells are deficient in ATM the cells are "addicted" to DNA-PKcs, important in the alternative DNA repair pathway for double-strand breaks, non-homologous end joining (NHEJ). (wikipedia.org)
  • In ATM mutant cells, additional loss of DNA-PKcs leaves the cells without either major pathway (HRR and NHEJ) for repair of DNA double-strand breaks. (wikipedia.org)
  • and that increased DNA repair facilitates greater longevity. (wikipedia.org)
  • As an example, they described a study showing that centenarians of 100 to 107 years of age had higher levels of two DNA repair enzymes, PARP1 and Ku70, than general-population old individuals of 69 to 75 years of age. (wikipedia.org)
  • Their analysis supported the hypothesis that improved DNA repair leads to longer life span. (wikipedia.org)
  • In humans and other mammals, DNA damage occurs frequently and DNA repair processes have evolved to compensate. (wikipedia.org)
  • Some DNA damage may remain in any cell despite the action of repair processes. (wikipedia.org)
  • nuclear
  • Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction). (wikipedia.org)
  • strands
  • As their family name suggests, a highly conserved tyrosine nucleophile cleaves the DNA strands. (wikipedia.org)
  • These other residues are crucial to the correct orientation of Flp binding and positioning on the DNA strands. (wikipedia.org)
  • recognition
  • The amino-terminus of the transposase, which contains the DNA-binding motifs for recognition of the direct repeats (DRs), was restored in steps 5->8. (wikipedia.org)
  • frequent
  • One of the most frequent lesions formed in cellular DNA are abasic (apurinic/apyrimidinic, AP) sites that are both cytotoxic and mutagenic, and must be removed efficiently to maintain genetic stability. (biomedsearch.com)
  • cytosine
  • Once unzipped, mismatched guanine and uracil pairs are separated, and DNA polymerase inserts complementary bases to form a guanine-cytosine (GC) pair in one daughter strand and an adenine-uracil (AU) pair in the other. (wikipedia.org)
  • pathways
  • Their importance is attested by the fact most organisms have multiple ligases dedicated to specific pathways of repairing DNA. (wikipedia.org)
  • catalytic
  • The three domains consist of an N-terminal DNA binding domain (DBD), and catalytic nucleotidyltransferase (NTase), and C-terminal oligonucleotide / oligosaccharide binding (OB) domains. (wikipedia.org)
  • Moreover, the identification of a cyclin binding (Cy) motif in the catalytic C-terminus domain was shown by mutational analysis to play a role in the phosphorylation of serines 91 and 76. (wikipedia.org)
  • lesions
  • citation needed] In estimates made for mice, DNA lesions occur on average 25 to 115 times per minute in each cell, or about 36,000 to 160,000 per cell per day. (wikipedia.org)
  • hypothesis
  • Hypothesis that aging is caused by accumulated DNA danage The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damages. (wikipedia.org)
  • covalently
  • 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)