• This single strand break is typically the substrate for DNA polymerase β (Pol β), which exerts DNA-deoxyribophosphodiesterase activity to cleave off the abasic sugar and uses the intact strand as template to synthesize the missing base ( 5 ). (pnas.org)
  • D, catalytic mechanism and dissociation/rate constants at 10 °C. The two alternative reaction pathways ( lower right ) produce 2OG turnover coupled to ( left branch ) or uncoupled from ( right branch ) DNA repair, depending on the relative rates of substrate hydroxylation versus release. (nih.gov)
  • We also propose that the inherent dynamics of the co‐product complex and the subsequent increased molecular ordering of the co‐substrate complex have a role in DNA damage recognition. (embopress.org)
  • Computational techniques of homology modelling, enzyme-substrate docking, and molecular dynamics were applied to elucidate the structure and substrate binding properties of the DNA repair enzyme polynucleotide kinase/phosphatase from the nematode C. elegans (CePNKP). (macewan.ca)
  • The substrate preference for both human and C. elegans PNKP has been investigated, and found to be similar, with higher selectivity for recessed over blunt DNA ends. (macewan.ca)
  • To elucidate the reason for the unique substrate specificity of CePNKP, the structure of CePNKP in complex with its DNA substrate must be determined in atomistic detail by molecular modelling. (macewan.ca)
  • Importantly, BER in the cell must take place on DNA in the context of chromatin. (pnas.org)
  • The primary level of chromatin packaging is the nucleosome core particle (NCP), consisting of 147 bp of DNA wrapped around an octamer of the four core histones H2A, H2B, H3, and H4 ( 11 ). (pnas.org)
  • Although the density of chromatin is an essential factor for its role in organizing DNA, its presence can be problematic for normal DNA metabolic processes, including DNA repair and transcription ( 8 , 10 , 12 - 15 ). (pnas.org)
  • Chromatin structure can be rearranged by ATP-dependant chromatin remodeling complexes which can remove, replace, and reposition nucleosomes along the DNA ( 17 ). (pnas.org)
  • The instance ATM and p400 : characterisation of a novel interaction between a DNA repair enzyme and a chromatin remodeler : a thesis presented to Massey University in partial fulfilment of the requirement for the degree of Doctor of Philosophy in Biochemistry, Rebecca Jane Smith represents a material embodiment of a distinct intellectual or artistic creation found in Massey University Library, University of New Zealand . (massey.ac.nz)
  • Studies of enzyme-initiated repair in bacteria have shown that using a microinjection technique to insert the enzyme into human cells increases the repair process. (cancernetwork.com)
  • Experiments led by MIT graduate student Daniel Jarosz and former postdoctoral fellow Veronica Godoy revealed that when bacteria that are missing DinB are exposed to a chemical that causes DNA damage, these bacteria are 1,000 times more likely to die than normal bacteria. (innovations-report.com)
  • Then graduate student Cynthia Kenyon, now a biologist at University of California, San Francisco who has done groundbreaking work on the genetic basis of aging in worms, systematically identified the genes turned on in bacteria exposed to DNA damaging agents, the so-called SOS response. (innovations-report.com)
  • If you inhibit the foreign enzyme in order to kill the bacteria, there is always a risk that this will affect the person s own enzymes, which leads to side-effects or even toxicity. (nanowerk.com)
  • However, we have discovered that the binding of molecules differs greatly between the human enzyme and the bacteria s RNR enzyme, so the risk of side-effects is therefore considerably smaller , says Derek Logan, senior lecturer at the Faculty of Science in Lund. (nanowerk.com)
  • In the study, the researchers also discovered that RNR from the type of bacteria that causes the sexually transmitted disease chlamydia has the same type of binding to the DNA building blocks. (nanowerk.com)
  • The genome encodes DNA repair enzymes homologous to those in both bacteria and eukaryotes. (wikipedia.org)
  • Recent methodological advances enable the contribution of protein dynamics to enzyme efficiency to be explored more deeply. (nih.gov)
  • Therefore, efficient catalysis by AlkB depends upon the dynamics of a specific conformational transition, establishing another paradigm for the control of enzyme function by protein dynamics. (nih.gov)
  • These conformational fluctuations allow for the replacement of succinate in the central core of the protein and probably contribute to the effective release of unmethylated DNA. (embopress.org)
  • The Ada protein is a multifunctional DNA methyltransferase that also acts as a transcriptional activator of the response. (embopress.org)
  • The exact function of AidB, a flavin‐binding protein, remains to be explained and AlkA is a DNA glycosylase with a broad specificity. (embopress.org)
  • Newswise - CHAPEL HILL, N.C. - Twelve years ago, UNC School of Medicine researcher Brian Strahl, PhD, found that a protein called Set2 plays a role in how yeast genes are expressed - specifically how DNA gets transcribed into messenger RNA. (newswise.com)
  • For instance, protein and DNA modifications involved in gene expression in kidneys must at some point be turned off. (newswise.com)
  • Here, we utilize enzymological and biophysical studies, including NMR measurements of conformational dynamics, to develop a quantitative mechanistic scheme for the DNA repair enzyme AlkB. (nih.gov)
  • Like other iron/2-oxoglutarate-dependent dioxygenases, AlkB employs a two-step mechanism in which oxidation of 2-oxoglutarate generates a highly reactive enzyme-bound oxyferryl intermediate that, in the case of AlkB, slowly hydroxylates an alkylated nucleobase. (nih.gov)
  • The 2‐oxoglutarate (2OG)‐ and Fe 2+ ‐dependent dioxygenase AlkB couples the demethylation of modified DNA to the decarboxylation of 2OG. (embopress.org)
  • Now his lab has found that Set2 is also a major player in DNA repair, a complicated and crucial process that can lead to the development of cancer cells if the repair goes wrong. (newswise.com)
  • As a photolyase, it depends on the capture of blue or ultraviolet (UV) light for its activity, the same radiation that causes DNA damage. (sciencephoto.com)
  • In this week's online edition of the Proceedings of the National Academy of Sciences , Ohio State physicist and chemist Dongping Zhong and his colleagues describe how they used ultra-fast pulses of laser light to spy on a photolyase while it was healing a strand of DNA. (osu.edu)
  • Now that we have accurately mapped the motions of a photolyase at the site of DNA repair, we can much better understand DNA repair at the atomic scale, and we can reveal the entire repair process with unprecedented detail," said Zhong, the Robert Smith Associate Professor of Physics, and associate professor in the departments of chemistry and biochemistry at Ohio State. (osu.edu)
  • Under those circumstances, an abasic site (a site where a base is missing) is left unrepaired, and so the DNA damage response kicks in, and kills the cell. (bio-medicine.org)
  • Pharmacogenetics of Cancer and DNA Repair Enzymes, DNA Repair and Human Health Sonya Vengrova, IntechOpen, DOI: 10.5772/23338. (intechopen.com)
  • Understanding how kangaroo DNA repairs itself could lead to preventing skin cancer. (cosmeticsandtoiletries.com)
  • Our focus has always been on DNA repair, and the most important outlet for DNA repair in oncology relates to skin cancer because this is the system in which we most clearly understand the carcinogen exposure to UV radiation," Daniel Yarosh, PhD, told ONI in an interview. (cancernetwork.com)
  • We began 15 years ago," Dr. Yarosh said, "with the idea of applying DNA repair technology in skin cancer prevention. (cancernetwork.com)
  • Some DNA repair enzymes can become double-edged swords If they work t...5FU has been used in cancer therapy for more than four decades and rem. (bio-medicine.org)
  • The work, published in this week's issue of PLoS Biology , reports that 5FU keeps the DNA-repair enzyme TDG too busy to perform properly in cancer cells, thereby promoting tumor death. (bio-medicine.org)
  • First author on the paper Christophe Kunz and his colleagues inactivated the TDG enzyme in different human and mouse cells and found that the cells became resistant to the cancer drug. (bio-medicine.org)
  • The finding, published online June 9 in the journal Nature Communications , is the first to show Set2's role in DNA repair and paves the way for further inquiry and targeted approaches to treating cancer patients. (newswise.com)
  • SETD2 plays such a critical role in DNA transcription and repair that Strahl is now teaming up with fellow UNC Lineberger Comprehensive Cancer Center members Stephen Frye, PhD, director of the UNC Center for Integrative Chemical Biology and Drug Discovery (CICBDD), Jian Jin, PhD, also with the CICBDD, and Kim Rathmell, MD, PhD, an associate professor in the department of genetics. (newswise.com)
  • If DNA isn't repaired correctly, then that can result in disastrous consequences for cells, one of them being increased mutation that can lead to cancer. (newswise.com)
  • DNA damage can cause cell death or cancer. (sciencephoto.com)
  • In humans, uncorrected DNA errors passed along to the new daughter cells can lead to cancer. (innovations-report.com)
  • Although these enzymatic steps can be accomplished by purified enzymes on naked DNA in vitro, there are accessory factors in cells, including XRCC1, that ensure efficiency and coordination of the repair process ( 6 , 7 ). (pnas.org)
  • There are two primary "active" mechanisms used by the cell, acting independently or in combination, to overcome the nucleosome-associated barriers to DNA metabolism. (pnas.org)
  • Mechanistic principles used for each repair strategies are fundamentally different. (asmscience.org)
  • H. salinarum is polyploid and highly resistant to ionizing radiation and desiccation, conditions that induce DNA double-strand breaks. (wikipedia.org)
  • Overexposure to sunlight reportedly is to blame for at least two-thirds of cases of melanoma since DNA in sunburned skin cells becomes damaged, leading to genetic mutations. (cosmeticsandtoiletries.com)
  • Through a series of biochemical and genetic experiments, Deepak Jha, a graduate student in Strahl's lab, was able to see what happens when cells experience a break in the double-strand of DNA. (newswise.com)
  • DNA carries a cell's genetic code. (sciencephoto.com)
  • Ultraviolet (UV) light damages skin by causing chemical bonds to form in the wrong places along the DNA molecules in our cells. (osu.edu)
  • Whereas U-Out NCPs show a cleavage rate just below that of naked DNA, U-In and U-Mid NCPs have markedly slower rates of cleavage. (pnas.org)
  • Crosslinking of U-In DNA to histones in NCPs yields a greater reduction in cleavage rate but, surprisingly, yields a higher rate of cleavage in U-Out NCPs compared with uncrosslinked NCPs. (pnas.org)
  • Moreover, the next enzyme in BER, APE1, stimulates the activity of human UDG in U-Out NCPs, suggesting these enzymes interact on the surface of histones in orientations accessible to UDG. (pnas.org)
  • CePNKP is a useful model system for studying the human enzyme. (macewan.ca)
  • However, CePNKP exhibits a more exclusive preference for recessed DNA ends than human PNKP. (macewan.ca)
  • In recent years, scientists have discovered the importance of how DNA is packaged inside nuclei. (newswise.com)
  • The enzyme has puzzled scientists because it is present in nearly every organism, which suggests that it is crucial to life, and yet, in laboratory experiments, its function has remained a mystery. (innovations-report.com)
  • These data indicate that the activity of UDG likely requires "trapping" transiently exposed states arising from the rotational dynamics of DNA on histones. (pnas.org)
  • The latter process is referred to as Translesion DNA Synthesis (TLS). (asmscience.org)
  • Hence, mice lacking PARP-1 or PARP-2 show DNA perturbations ranging from altered DNA integrity to impaired DNA repair. (pasteur.fr)
  • Examination of TIP60 domains and p400 SANTdomain helix deletion mutants in the DNA damage response -- 4. (massey.ac.nz)
  • FREEPORT, NY In a phase III clinical trial of 30 patients with xeroderma pigmentosum, use of a topically applied DNA repair enzyme (T4N5 liposome lotion) for 1 year reduced the incidence of basal cell carcinoma by 30% and actinic keratoses by 68%, compared with placebo. (cancernetwork.com)
  • Because the AP site repair intermediate is a liability to the cell, some glycosylases are retained at the site with high affinity, released only when the next factor in BER, the AP endonuclease (APE1), is available ( 4 ). (pnas.org)
  • Some DNA repair enzymes can become double-edged swords If they work too slowly, they can block necessary cell maintenance and contribute to cell death. (bio-medicine.org)
  • Furthermore, the same TgMSH-1 dependent cell cycle disruption is observed with the anti-parasitic ionophore salinomycin and the DNA alkylating agent methyl nitrosourea. (blogspot.com)
  • The DNA in each cell is damaged 2000-10,000 times a day by hydrolysis reactions which convert N-glycosyl bonds to apurinic/apyrimidinic breaks. (sciencephoto.com)
  • The primary role of bacterioruberin in the cell is to protect against DNA damage incurred by UV light. (wikipedia.org)
  • In addition, histones are targeted for a wide range of posttranslational modifications, including methylation and acetylation, which can alter DNA-histone interactions and/or "mark" NCPs, for recognition, to aid additional activities ( 10 ). (pnas.org)
  • DNA is assaulted daily by toxic chemicals, metabolic byproducts, sunlight, and other forms of radiation. (innovations-report.com)
  • These nucleosome cores are located in close proximity along the chromosomes, separated by short, variable lengths of "linker" DNA (∼20-90 bp), which are bound by either of the linker histones H1 or H5. (pnas.org)