74 research outputs found
7 DNA-dependent protein kinase and related proteins
No full textThe DNA-dependent protein kinase (DNA-PK) is a nuclear protein serine/threonine kinase that must bind to DNA double-strand breaks to be active. We and others have shown that it is a multiprotein complex comprising an approx. 465 kDa catalytic subunit (DNA-PKcs) and a DNA-binding component, Ku. Notably, cells defective in DNA-PK are hypersensitive to ionizing radiation. Thus X-ray-sensitive hamster xrs-6 cells are mutated in Ku, and rodent V3 cells and cells of the severe combined immune-deficient (Scid) mouse lack a functional DNA-PKcs. Cloning of the DNA-PKcs cDNA revealed that it falls into the phosphatidylinositol (PI) 3-kinase family of proteins. However, biochemical assays indicate that DNA-PK contains no intrinsic lipid kinase activity, but is instead a serine/threonine kinase. We have also found that DNA-PK activity can be inhibited by the PI 3-kinase inhibitors wortmannin and LY294002. Consistent with its proposed role in genome surveillance and the detection of DNA damage, DNA-PKcs is most similar to a subset of proteins involved in cell-cycle checkpoint control and signalling of DNA damage. Furthermore, the recent cloning of the gene mutated in ataxia-telangiectasia (A-T) patients, named ATM (A-T mutated), has revealed that the product of this gene is also a PI 3-kinase family member and is related to DNA-PKcs. Although much is known about the clinical symptoms and cellular phenotypes that arise from disruption of the A-T gene, little is known about the biochemical action of ATM in response to DNA damage. Given its sequence similarity with DNA-PKcs, we speculate that ATM may function in a manner similar to DNA-PK
Recruitment of 9-1-1 to sites of DNA damage through cell cycle-dependent processing of DNA lesions.
No full textDictyostelium discoideum as a model to assess genome stability through DNA repair
No full textPreserving genome integrity through repair of DNA damage is critical for human health and defects in these pathways lead to a variety of pathologies, most notably cancer. The social amoeba Dictyostelium discoideum is remarkably resistant to DNA damaging agents and genome analysis reveals it contains orthologues of several DNA repair pathway components otherwise limited to vertebrates. These include the Fanconi Anaemia DNA inter-strand crosslink and DNA strand break repair pathways. Loss of function of these not only results in malignancy, but also neurodegeneration, immune-deficiencies and congenital abnormalities. Additionally, D. discoideum displays remarkable conservations of DNA repair factors that are targets in cancer and other therapies, including poly(ADP-ribose) polymerases (PARPs) that are targeted to treat breast and ovarian cancers. This, taken together with the genetic tractability of D. discoideum, make it an attractive model to assess the mechanistic basis of DNA repair to provide novel insights into how these pathways can be targeted to treat a variety of pathologies. Here we describe progress in understanding the mechanisms of DNA repair in D. discoideum, and how these impact on genome stability with implications for understanding development of malignancy
Redundancy between nucleases required for homologous recombination promotes PARP inhibitor resistance in the eukaryotic model organism Dictyostelium
No full textThe Midwest Quarterly; Vol. 2 No. 2
No full textin this issue. . .
THIS is a historic month, and the editors of THE MIDWEST QUARTERLY have perforce taken this fact into account in selecting the material appearing in this issue. The presidential elections are behind us, and a new national administration will be inaugurated on the twentieth of this month. On the twenty-ninth, Kansans will observe the centennial of statehood and inaugurate a year of celebrations of all sorts for this important midwest milestone. In a sense, this month of January, 1961, is a meeting point for the Old Frontier of the Kansas past and the New Frontiers of John F. Kennedy. At the same time, of course, in the world around us a complex of problems continues to face the American people. Prominent in that complex are both the difficult problem of East-West relations and the equally thorny problem of the treatment of minority ethnic and national groups. We have articles analyzing and discussing various aspects of both of these. Of the seven contributors to this issue, three have already been introduced to our readers, while the remaining four are new.
THE PRESIDENCY of the United States has attracted the attention of political scientists on both sides of the Atlantic for well over a century now. Among those who have studied the presidency as office, institution, and symbol, is ALVIN H. PRocroR, Dean of Graduate Studies and professor of political science at Kansas State College of Pittsburg. The initial article in this issue is his synthesis of a wide assortment of analyses and observations on the American presidency, a synthesis enriched by his own study and experience. Long a student of American and British politics, teaching courses in American government, political parties, and both American and British history, Dean Proctor holds bachelor\u27s and master\u27s degrees from this College and the doctor of philosophy from the University of Wisconsin. Since 1948 he has been a member of this College faculty. In 1950 he became chairman of the Department of Social Science, and in 1959 he was appointed to his present position. In 1954 he was awarded a Ford Faculty Fellowship enabling him to study at Harvard University and to examine international politics at the United Nations in New York and national politics in Washington, D. C. Readers of THE MIDWEST QUARTERLY will recall his article in our first issue ( October, 1959), Power Factors in Kansas Constitutional Revision. His present contribution was originally prepared as the first in the 1960-61 series of Great Issues Lectures under the sponsorship of the Department of Social Science.
KANSAS has challenged and baffled interpretation for more than a century. Senator Charles Sumner of Massachusetts had so much to say about Kansas in the spring of 1856 and said it in such a heated and extravagant way that Preston Brooks of South Carolina very nearly beat him to death with a cane. Fortunately, not all who have talked and written about Kansas have been so treated. Artemus Ward, for example, managed to survive his suggestion that Kansas ought to be wiped off the map! The late great Carl Becker of Cornell wrote entertainingly on the subject, the young William Allen White of Emporia wrote passionately about what he considered to be the matter with Kansas, and recent historiography on the coming of the Civil War has been made bloody by whole chapters on the various crimes committed either by or against Kansas and Kansans. With the centennial of Kansas statehood just beginning, we can anticipate a great outpouring of material--good, bad, and indifferent--on, about, and by Kansas and Kansans. For our first contribution to the celebration of the centennial, we have been fortunate in securing an article by a transplanted Kansan, JACK WARNER VANDERHOOF, professor of history and political science and chairman of the social sciences division at Kansas Wesleyan University, Salina. Professor VanDerhoof joined the faculty at Kansas Wesleyan ten years ago after completing graduate study and the doctor of philosophy degree at Columbia University. He did his undergraduate work at Drew University in Madison, New Jersey. His article is an outgrowth of, first, a paper read last March before the Third Annual Missouri Valley Conference of Collegiate Teachers of History at the University of Omaha and, second, the first of the 1960-61 Memorial Library Lecture Series at Kansas Wesleyan. These lectures, by members of the faculty there, are, according to public announcement, intended to be provocative of thinking about Kansas and Kansans in this, our Centennial Year. We think that Professor VanDerhoof\u27s article here published meets this specification rather well.
OUR POETS contributing to this issue are LEWIS TURCO whose A Hollow Rush appeared in our July issue, and MADELINE MASON, author and critic of Tannersville, New York. When his work first appeared in THE MIDWEST QUARTERLY, Mr. Turco was a graduate student at the State University of Iowa in Iowa City where he took the Academy of American Poets prize in 1960. After a summer in his home hills of Connecticut, he began a new assignment as instructor in English and creative writing at Fenn College in Cleveland, Ohio. Apparently he did not rusticate last summer but followed his craft diligently with the result that new poetic work of his will appear in forthcoming issues of The Minnesota Review, Paris Review, Perspective, and Poetry. In one of his contributions to this issue, Mr. Turco employs Anglo-Saxon prosody with obvious emphasis on alliteration; he has written the other, The Dancer, in an accentual form called the triversen.
Miss Mason has a distinguished literary history including a variety of poetic and prose productions: Hill Fragments,1925; Riding for Texas (with Colonel E. M. House), 1936; The Cage of Years, 1949, and At the Ninth Hour, 1957; in that year she received the Diamond Jubilee Award of the National League of American Pen Women. She has also translated into French The Prophet of Kahlil Gibran and has written radio scripts and a syndicated political column. Her works have appeared in a variety of national magazines, and she has participated in the Buffalo University Lectures and the Edinburgh Festival of 1953. A member of the Poetry Society of America, she recorded selections from her work for the Library of Congress in 1956. She spends her summers at Casa Benita, Onteora Park, near Tannersville in the Catskill Mountains where she was visited last August by our own Charles Burgess, two of whose poems appeared in our July issue.
SOVIET RUSSIA still remains almost as much an enigma as Sir Winston Churchill found it during World War II, but more arid more information and speculation about various aspects of current Russian life appear, particularly as the lines of cultural communication between Russia and the West are broadened and deepened. The third and fourth articles in this issue fit rather nicely the foregoing generalization. KAREL HULICKA, assistant professor of history and government at the University of Buffalo since 1959, has contributed a valuable discussion of Soviet methodology and philosophy with regard to the difficult problem arising from the multinational character of the Russian people.
Professor Hulicka was born in Prague, Czechoslovakia, where he attended the Academy of Commerce and the University of Prague. He was graduated from the former with a diploma summa cum laude and from the latter with an advanced degree in economics. He holds the doctor of philosophy in political science from the University of California, Berkeley. A member of the American Political Science Association and the American Association for the Advancement of Slavic Studies, he has taught at the universities of California, Minnesota, and Oklahoma. His previous publications included articles in a variety of journals including Land Economics Soviet Studies, The Journal of Politics, The Psychological Record, and The Southwestern Social Science Quarterly, to name a few. In addition, he is co-author of a textbook on European comparative government and has contributed to The Encyclopedia Americana and The Social Studies, all three works currently in press.
RELATIONS between the Soviet hierarchy and what Rudyard Kipling might at one time have called the sullen, subject peoples making up the Russian population constitute a difficult problem, but one which Professor Hulicka seems to think is fairly close to a reasonable solution. Relations between Soviet Russia and the rest of the world, particularly scholarly interchange, make for a tougher problem for which no easy solution offers itself. Last summer the editors of THE MIDWEST QUARTERLY received a manuscript from Cripple Creek, Colorado, a manuscript bearing the interesting title Mark Twain and the Cold War. Examination quickly disclosed that our man in Cripple Creek was none other than R. D. LAKIN whose work first appeared in our July issue. Mr. Lakin is an instructor in the Department of Language and Literature here but his interests run more toward philosophy than rhetoric. Last summer while vacationing and studying on the far side of the American Urals, he read a recent pamphlet, Mark Twain and the Russians, edited by Charles Neider who has done a great deal of work on Samuel L. Clemens, particularly as editor of Twain\u27s Autobiography. Since Mr. Lakin is primarily concerned with all phases of criticism and art, especially the literary art, he was drawn into the controversy currently raging between Mr. Neider and Mr. Yan Bereznitsky, critic for the Russian Literary Gazette. The result of Mr. Lakin\u27s involvement and concern for this ideological conflict seems to the editors to make a good companion-piece for Professor Hulicka\u27s article because it points up some basic aspects of the problem of scholarly communication through the Iron Curtain.
WHILE MARK TWAIN is probably the best known figure in American literature, the name of Herman Melville has gained luster in recent decades to a point where his growing stature almost overshadows all other American literary artists. When one considers Melville\u27s life, which falls roughly into two major periods--the first bright with early success, the second dark with despair, disillusion, and neglect--his emergence as a major figure on the American scene a half century after his death becomes the more amazing. But, on the other hand, is not the Melville case typical of many of our American literary giants? Many of the writings of Mark Twain were long considered juvenile literature and have been so published, even with pretty pictures of Tom and Huck. So to a great extent with Herman Melville: even the great Moby Dick was long considered a sea-adventure story for boys. The recent history of American literature is filled with rediscoveries of neglected aspects and overlooked levels of content, theme, and symbolism. In his survey of Melville criticism, DAVID D. ANDERSON provides an illuminating study of the different ways in which reviewers have read Melville, particularly his White Jacket. Professor Anderson has the doctor of philosophy in American literature; his primary fields of interest are nineteenth and twentieth century intellectual history. He has published short stories as well as numerous articles on Emerson, Margaret Fuller, Lincoln, Poe, and Whitman; these have appeared in various periodicals. At present he is teaching American language and thought at Michigan State University, East Lansing
IS REALLY A DIFFUSE INTERSTELLAR BAND CARRIER?
No full textSupported by the Fannie and John Hertz Foundation M. Tulej, D. A. Kirkwood, M. Pachkov, \& J. P. Maier, Astrophysical Journal Letters 506, L69 (1998) B. J. McCall, D. G. York, \& T. Oka, Talk RF09, 54th International Symposium on Molecular Spectroscopy B. J. McCall, D. G. York, \& T. Oka, Astrophysical Journal 531, 329 (2000) N. M. Lakin, M. Tulej, M. Pachkov, F. G\""uthe \& J. P. Maier, Talk TC02, 55th International Symposium on Molecular Spectroscopy N. M. Lakin, M. Pachkov, M. Tulej, J. P. Maier, G. Chambaud, \& P. Rosmus, Journal of Chemical Physics 113, 9586 (2000)Author Institution: University of Chicago; Department of Chemistry, Department of Astronomy \& Astrophysics, and the Enrico Fermi Institute, University of ChicagoPerhaps the longest standing unsolved problem in molecular spectroscopy is that of the Diffuse Interstellar Bands (DIBs) --- a series of hundreds of absorption lines present in the spectra of nearly all stars which lie behind sufficient quantities of interstellar material. Despite the fact that the first of the DIBs were observed nearly 100 years ago, none of them can yet be attributed with confidence to a molecule whose spectrum has been obtained in the laboratory. Many astronomers and spectroscopists were hopeful that this impasse had finally been broken when John Maier's group the gas-phase laboratory spectrum of . Based on the best atlas of DIBs available at the time, the five strongest transitions of the band seemed a promising match. Using the new high resolution () echelle spectrometer on the 3.5 m telescope at the Apache Point Observatory, we have begun a high sensitivity survey of DIBs in a large sample of reddened stars. A preliminary analysis of the `` bands'' in four stars in our sample was reported at the 1999 and subsequently . Now that we are two years into our long-term survey, our sample includes over 20 reddened stars, with at least some of the `` bands'' detected in more than 15 of them. In this talk, we re-examine the correlation between the candidate DIBs to see if they are caused by the same molecule. We also discuss the wavelength agreement between the laboratory and interstellar measurements, as well as our astronomical search for the components of the bands recently identified in the laboratory
Recruitment of ATR to sites of ionising radiation-induced DNA damage requires ATM and components of the MRN protein complex.
No full textATM and ATR are two related kinases essential for signalling DNA damage. Although ATM is thought to be the principle kinase responsible for signalling ionising radiation (IR)-induced DNA damage, ATR also contributes to signalling this form of genotoxic stress. However, the molecular basis of differential ATM and ATR activation in response to IR remains unclear. Here, we report that ATR is recruited to sites of IR-induced DNA damage significantly later than activation of ATM. We show that ATR is recruited to IR-induced nuclear foci in G(1) and S phase of the cell cycle, supporting a role for ATR in detecting DNA damage outside of S phase. In addition, we report that recruitment of ATR to sites of IR-induced DNA damage is concomitant with appearance of large tracts of single-stranded DNA (ssDNA) and that this event is dependent on ATM and components of the Mre11/Rad50/Nbs1 (MRN) protein complex
Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase.
No full textThe ataxia telangiectasia-mutated (ATM) and Rad3-related kinase (ATR) is a central component of the cell cycle checkpoint machinery required to induce cell cycle arrest in response to DNA damage. Accumulating evidence suggests a role for ATR in signaling DNA damage during S-phase. Here we show that ATR is recruited to nuclear foci induced by replication fork stalling in a manner that is dependent on the single stranded binding protein replication protein A (RPA). ATR associates with chromatin in asynchronous cell cultures, and we use a variety of approaches to examine the association of ATR with chromatin in the absence of agents that cause genotoxic stress. Under our experimental conditions, ATR exhibits a decreased affinity for chromatin in quiescent cells and cells synchronized at mitosis but an increased affinity for chromatin as cells re-enter the cell cycle. Using centrifugal elutriation to obtain cells enriched at various stages of the cell cycle, we show that ATR associates with chromatin in a cell cycle-dependent manner, specifically during S-phase. Cell cycle association of ATR with chromatin mirrors that of RPA in addition to claspin, a cell cycle checkpoint protein previously shown to be a component of the replication machinery. Furthermore, association of ATR with chromatin occurs in the absence of detectable DNA damage and cell cycle checkpoint activation. These data are consistent with a model whereby ATR is recruited to chromatin during the unperturbed cell cycle and points to a role of ATR in monitoring genome integrity during normal S-phase progression
HIGH RESOLUTION INFRARED SPECTROSCOPY IN A SUPERSONIC PLANAR PLASMA
No full text[1] H.E. Verbraak, J. Bouwman, J. de Klerk, H. Linnartz, Int. J. Mass Spectrom., in preparation. [2] H. Linnartz, D. Verdes, J.P. Maier, Science 297 (2002) 1166. [3] H. Linnartz, D. Verdes, P.J. Knowles, N.M. Lakin, P. Rosmus, J.P. Maier, J. Chem. Phys. 113 (2000) 895.Author Institution: Department of Physical Chemistry, Laser Centre Vrije UniversiteitA mass spectrometric and laser spectroscopic experiment has been performed to study high resolution infrared spectra of small cluster ions. The method is based on direct absorption of tunable diode laser radiation in an expansion cooled planar plasma. The plasma is generated by electron impact ionization of gas that is expanded supersonically through a long and narrow slit. This technique allows a fast and effective production modulation. The setup has recently been reassembled and improved in a number of aspects [1]. New results are shown for the charge transfer complex and the Ar-ion sandwich , that were studied in detail previously [2,3]
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