Abstract:
:DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis.
journal_name
Proc Natl Acad Sci U S Aauthors
Izhar L,Ziv O,Cohen IS,Geacintov NE,Livneh Zdoi
10.1073/pnas.1216894110subject
Has Abstractpub_date
2013-04-16 00:00:00pages
E1462-9issue
16eissn
0027-8424issn
1091-6490pii
1216894110journal_volume
110pub_type
杂志文章abstract::We have used germ-line transformation to dissect the cis regulatory elements responsible for the transcriptional control of an internally marked Drosophila chorion gene (s15-P) during development. A 73-base-pair segment of the proximal 5'-flanking DNA contains sequences essential for the tissue-specific expression and...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.9.3029
更新日期:1988-05-01 00:00:00
abstract::Zebrafish carrying heterozygous mutations for 17 different ribosomal protein (rp) genes are prone to developing malignant peripheral nerve sheath tumors (MPNSTs), a tumor type that is seldom seen in laboratory strains of zebrafish. Interestingly, the same rare tumor type arises in zebrafish that are homozygous for a l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0805036105
更新日期:2008-07-29 00:00:00
abstract::The sex pheromone biosynthetic pathways of lepidopterans require the concerted actions of multiple gene products. A number of pheromone gland (PG)-specific genes have been cloned in recent years and, whereas in vitro characterizations have indicated functions consistent with roles in pheromone production, there have b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0511270103
更新日期:2006-03-21 00:00:00
abstract::Isolated yeast mitochondria, which synthesize identifiable polypeptides identical to those made in vivo, have been used in an invitro system to study cytoplasmic control of mitochondrial protein synthesis. It has been found that protein synthesis in isolated mitochondria is dependent on an endogenous pool of cytoplasm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.11.3947
更新日期:1976-11-01 00:00:00
abstract::In recent years, considerable progress has been made in understanding the molecular mechanisms underlying olfaction in insects. Because of the diverse nature of the gene families involved, this process has largely relied on genomic data. As a consequence, studies have focused on a small subset of species with extensiv...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1017963108
更新日期:2011-05-03 00:00:00
abstract::The ever-increasing industrial demand for nylon-6 (polycaprolactam) necessitates the development of environmentally benign methods of producing its precursor, epsilon-caprolactam, from cyclohexanone. It is currently manufactured in two popular double-step processes, each of which uses highly aggressive reagents, and e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506907102
更新日期:2005-09-27 00:00:00
abstract::Human P-glycoprotein (Pgp) confers multidrug resistance to cancer cells by ATP-dependent extrusion of a great many structurally dissimilar hydrophobic compounds. The manner in which Pgp recognizes these different substrates is unknown. The protein shows internal homology between its N- and C-terminal halves, each comp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.20.10594
更新日期:1997-09-30 00:00:00
abstract::Molecular cloning has established the primary structures of two precursors of the human pancreas growth hormone-releasing factor (hpGRF-44), somatocrinin. Both polypeptides contain the sequence of hpGRF-44 flanked by basic processing sites. Furthermore, the precursors include a putative signal sequence and a carboxyl-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.14.4311
更新日期:1983-07-01 00:00:00
abstract::Calcicludine (CaC) is a 60-amino acid polypeptide from the venom of Dendroaspis angusticeps. It is structurally homologous to the Kunitz-type protease inhibitor, to dendrotoxins, which block K+ channels, and to the protease inhibitor domain of the amyloid beta protein that accumulates in Alzheimer disease. Voltage-cla...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.3.878
更新日期:1994-02-01 00:00:00
abstract::Extensive utilization of pesticides against insects provides us with a good model for studying the adaptation of a eukaryotic genome to a strong selective pressure. One mechanism of resistance is the alteration of acetylcholinesterase (EC 3.1.1.7), the molecular target for organophosphates and carbamates. Here, we rep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.13.5922
更新日期:1994-06-21 00:00:00
abstract::The IgG2a monoclonal antibody TH-1, which reacts specifically with blood group A1 but with neither A2 nor O erythrocytes, has been established. The antibody reacted only with A1 erythrocytes in hemagglutination and antibody absorption assays; it did not react with A2 erythrocytes, even after trypsin or sialidase treat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.4.1199
更新日期:1985-02-01 00:00:00
abstract::Spider-like forms of purified reovirus RNA have been characterized by electron microscopy. These structures contained 11.3 +/- 0.8 mum of double-stranded RNA and up to 20 arms, each of distinct length. Length measurements of 64 "spiders" suggest that in these structures the viral genome is folded fairly specifically. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.11.4317
更新日期:1975-11-01 00:00:00
abstract::Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, inta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.4.2562
更新日期:1981-04-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) cells (PCC) have an exceptional propensity to metastasize early into intratumoral, chemokine-secreting nerves. However, we hypothesized the opposite process, that precancerous pancreatic cells secrete chemokines that chemoattract Schwann cells (SC) of nerves and thus induce read...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1606909114
更新日期:2017-01-03 00:00:00
abstract::Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles. We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.161272598
更新日期:2001-07-17 00:00:00
abstract::Neurobiological theories of awareness propose divergent accounts of the spatial extent of brain changes that support conscious perception. Whereas focal theories posit mostly local regional changes, global theories propose that awareness emerges from the propagation of neural signals across a broad extent of sensory a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1414466112
更新日期:2015-03-24 00:00:00
abstract::Microtubule assembly is enhanced by the addition of 1 M sucrose or 4 M glycerol to the reassembly mixture. Tubulin can be purified from guinea pig brain readily and in good yield by two cycles of assembly in glycerol-containing solutions. The tubules assembled in glycerol and sucrose are more stable than tubules forme...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.3.765
更新日期:1973-03-01 00:00:00
abstract::We have studied the effects of food restriction (FR) and substitution of fish oil (FO; omega 3) for corn oil (CO; omega 6) on breast tumor incidence and survival in mouse mammary tumor virus/v-Ha-ras transgenic (Onco) mice. The diets were as follows: group 1, 5% (wt/wt) CO fed ad libitum (AL); group 2, 5% CO, restrict...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.14.6494
更新日期:1995-07-03 00:00:00
abstract::We have used the polymerase chain reaction (PCR) to amplify up to 22 kb of the beta-globin gene cluster from human genomic DNA and up to 42 kb from phaga lambda DNA. We have also amplified 91 human genomic inserts of 9-23 kb directly from recombinant lambda plaques. To do this, we increased pH, added glycerol and dime...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.12.5695
更新日期:1994-06-07 00:00:00
abstract::A modified differential screening procedure was applied to analyze cDNA libraries of cloned helper T lymphocytes (Th) and cytolytic T lymphocytes (CTL). Negative and positive differential screening and RNA blot analysis were used to identify cDNA clones that were expressed preferentially in Th or CTL. Seven clones cor...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.9.2896
更新日期:1987-05-01 00:00:00
abstract::Soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) protein interactions at the synaptic vesicle/plasma membrane interface play an essential role in neurotransmitter release. The membrane-proximal region (amino acids 77-90) of the v-SNARE vesicle-associated membrane protein 2 (VAMP 2,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0303274101
更新日期:2004-02-10 00:00:00
abstract::Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1700465115
更新日期:2018-01-23 00:00:00
abstract::The development of anther and pollen is important for male reproduction, and this process is coordinately regulated by many external and internal cues. In this study, we systematically examined the male reproductive phenotypes of a series of brassinosteroid biosynthetic and signaling mutants and found that, besides th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0912333107
更新日期:2010-03-30 00:00:00
abstract::A screening procedure based on solvent extraction with minimal clean up followed by examination with negative chemical ionization mass spectrometry has been developed for organochlorine residues and related compounds with masses greater than 130 daltons. The procedure has been made quantitative for analysis of pentach...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.6.1777
更新日期:1976-06-01 00:00:00
abstract::Phytocannabinoids, such as the principal bioactive component of marijuana, delta9-tetrahydrocannabinol, have been used for thousands of years for medical and recreational purposes. delta9-Tetrahydrocannabinol and endogenous cannabinoids (e.g., anandamide) initiate their agonist properties by stimulating the cannabinoi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0507470102
更新日期:2005-12-06 00:00:00
abstract::The ability of long-term cultured and monoclonal T cell populations to provide antigen-specific help was assessed in a system of Ir gene-controlled in vitro antibody responses to soluble antigens. T-cell colonies and monoclonal T-cell lines were generated which proliferated specifically in response to poly(LTyr,Glu)-p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.10.6431
更新日期:1981-10-01 00:00:00
abstract::We have previously shown that lymphoblasts alloactivated in vitro acquire the capacity of stimulating the autologous mixed lymphocyte response. This response is anti-idiotypic in nature because lymphocytes so primed display accelerated memory responses only when restimulated by autologous lymphoblasts that have been a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.3.830
更新日期:1983-02-01 00:00:00
abstract::Spantide (D-Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-D-Trp7-Phe8-D-Trp9-++ +Leu10-Leu11-NH2) was introduced as a tachykinin antagonist in 1984 and has served as a starting point in the design of new antagonists that have proven to be more effective and have exhibited no neurological side effects. The most remarkable and unpredic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.12.4833
更新日期:1990-06-01 00:00:00
abstract::Homologous recombination is an important biological process that occurs in all organisms and facilitates genome rearrangements and repair of DNA double-strand breaks. Eukaryotic Rad51 proteins (Rad51sp or Rhp51 in fission yeast) are functional and structural homologs of bacterial RecA protein, an evolutionarily conser...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2632890100
更新日期:2003-12-23 00:00:00
abstract::Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood. Here we report that mammary tumors induced by components of the Wnt signaling pathway contain heterogeneous cell types an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2136825100
更新日期:2003-12-23 00:00:00