Davis, Brian M., Encell, Lance P., Zielske, Steven P., Christians, Fred C., Liu, Lili, Friebert, Sarah E., ...
Applied molecular evolution is a rapidly developing technology that can be used to create and identify novel enzymes that nature has not selected. An important application of this technology is the...
Nuclear DNA polymerase of sea urchin embryos. (1967)
Thesis (Ph. D. in Comparative Biochemistry)--Univ. of California, Berkeley, Sept. 1967.
Lethal mutagenesis of HIV with mutagenic nucleoside analogs
Loeb, Lawrence A., Essigmann, John M., Kazazi, Farhad, Zhang, Jue, Rose, Karl D., Mullins, James I.
The human immunodeficiency virus (HIV) replicates its genome and mutates at exceptionally high rates. As a result, the virus is able to evade immunological and chemical antiviral agents. We tested...
Rink, Stacia M., Shen, Jiang-Cheng, Loeb, Lawrence A.
We used in vitro evolution to obtain RNA molecules that specifically recognize and bind with high affinity to the oxidative lesion 7,8-dihydro-8-hydroxy-2′-deoxyguanosine (8-oxodG) in DNA. A pool...
Induction of microsatellite instability by oxidative DNA damage
Jackson, Aimee L., Chen, Ru, Loeb, Lawrence A.
Instability of repetitive sequences, both in intronic sequences and within coding regions, has been demonstrated to be a hallmark of genomic instability in human cancer. Understanding how these...
DNA polymerase active site is highly mutable: Evolutionary consequences
Patel, Premal H., Loeb, Lawrence A.
DNA polymerases contain active sites that are structurally superimposable and highly conserved in sequence. To assess the significance of this preservation and to determine the mutational burden that...
Davis, Brian M., Encell, Lance P., Zielske, Steven P., Christians, Fred C., Liu, Lili, Friebert, Sarah E., ...
Applied molecular evolution is a rapidly developing technology that can be used to create and identify novel enzymes that nature has not selected. An important application of this technology is the...
Enzymatic properties of rat DNA polymerase β mutants obtained by randomized mutagenesis
Skandalis, Adonis, Loeb, Lawrence A.
We have used random sequence mutagenesis to generate mutants of DNA polymerase β in an effort to identify amino acid residues important for function, catalytic efficiency and fidelity of...
Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA
Shen, Jiang-Cheng, Loeb, Lawrence A.
Werner syndrome (WS) is an autosomal recessive disease characterized by early onset of many features of aging, by an unusual spectrum of cancers, and by genomic instability. The WS protein (WRN)...
Mutations in human DNA polymerase η motif II alter bypass of DNA lesions
Glick, Eitan, Vigna, Kellie L., Loeb, Lawrence A.
Human DNA polymerase η (hPolη) is one of the newly identified Y-family of DNA polymerases. These polymerases synthesize past template lesions that are postulated to block replication fork...
Davidson, John F., Fox, Richard, Harris, Dawn D., Lyons-Abbott, Sally, Loeb, Lawrence A.
Insertion of the T3 DNA polymerase thioredoxin binding domain (TBD) into the distantly related thermostable Taq DNA polymerase at an analogous position in the thumb domain, converts the Taq DNA...
Targeted gene evolution in Escherichia coli using a highly error-prone DNA polymerase I
Camps, Manel, Naukkarinen, Jussi, Johnson, Ben P., Loeb, Lawrence A.
We present a system for random mutagenesis in Escherichia coli for the evolution of targeted genes. To increase error rates of DNA polymerase I (Pol I) replication, we introduced point mutations in...
Tumbling down a different pathway to genetic instability
Guo, Haiwei H., Loeb, Lawrence A.
Ulcerative colitis (UC), a chronic inflammatory condition associated with a predisposition to colon cancer, is frequently characterized by DNA damage in the form of microsatellite instability (MSI)....
Loeb, Lawrence A., Loeb, Keith R., Anderson, Jon P.
Most human tumors are highly heterogenous. We have hypothesized that this heterogeneity results from a mutator phenotype. Our premise is that normal mutation rates are insufficient to account for the...
DNA polymerase activity as an index of lymphocyte stimulation: studies in Down's syndrome
Agarwal, S. S., Blumberg, Baruch S., Gerstley, Betty Jane S., London, W. Thomas, Sutnick, Alton I., Loeb, Lawrence A.
The ability of peripheral blood lymphocytes to respond to phytohemagglutinin (PHA) in vitro was studied in patients with Down's syndrome. The response was measured by the increase in DNA polymerase...
Mutagenic DNA Polymerase in Human Leukemic Cells
Springgate, Clark F., Loeb, Lawrence A.
Evidence is presented that DNA polymerases from human leukemic cells are mutagenic. Nucleic acid-free extracts of acute lymphoblastic leukemic cells polymerized about 10-times more dCTP using...
Reverse Transcriptase: Correlation of Zinc Content with Activity
Poiesz, Bernard J., Seal, Gita, Loeb, Lawrence A.
Evidence is presented that DNA polymerase of avian myeloblastosis virus has an obligatory zinc requirement for activity. Previous studies indicate that the purified polymerase contains zinc in a...
Protein tolerance to random amino acid change
Guo, Haiwei H., Choe, Juno, Loeb, Lawrence A.
Mutagenesis of protein-encoding sequences occurs ubiquitously; it enables evolution, accumulates during aging, and is associated with disease. Many biotechnological methods exploit random mutations...
Khateb, Samer, Weisman-Shomer, Pnina, Hershco, Inbal, Loeb, Lawrence A., Fry, Michael
Hairpin or tetrahelical structures formed by a d(CGG)n sequence in the FMR1 gene are thought to promote expansion of the repeat tract. Subsequent to this expansion FMR1 is silenced and fragile X...
Negative Clonal Selection in Tumor Evolution
Beckman, Robert A., Loeb, Lawrence A.
Development of cancer requires the acquisition of multiple oncogenic mutations and selection of the malignant clone. Cancer evolves within a finite host lifetime and mechanisms of carcinogenesis that...
Lethal mutagenesis of HIV with mutagenic nucleoside analogs
Loeb, Lawrence A., Essigmann, John M., Kazazi, Farhad, Zhang, Jue, Rose, Karl D., Mullins, James I.
The human immunodeficiency virus (HIV) replicates its genome and mutates at exceptionally high rates. As a result, the virus is able to evade immunological and chemical antiviral agents. We tested...
Rink, Stacia M., Shen, Jiang-Cheng, Loeb, Lawrence A.
We used in vitro evolution to obtain RNA molecules that specifically recognize and bind with high affinity to the oxidative lesion 7,8-dihydro-8-hydroxy-2′-deoxyguanosine (8-oxodG) in DNA. A pool...
Induction of microsatellite instability by oxidative DNA damage
Jackson, Aimee L., Chen, Ru, Loeb, Lawrence A.
Instability of repetitive sequences, both in intronic sequences and within coding regions, has been demonstrated to be a hallmark of genomic instability in human cancer. Understanding how these...
DNA polymerase active site is highly mutable: Evolutionary consequences
Patel, Premal H., Loeb, Lawrence A.
DNA polymerases contain active sites that are structurally superimposable and highly conserved in sequence. To assess the significance of this preservation and to determine the mutational burden that...
Davis, Brian M., Encell, Lance P., Zielske, Steven P., Christians, Fred C., Liu, Lili, Friebert, Sarah E., ...
Applied molecular evolution is a rapidly developing technology that can be used to create and identify novel enzymes that nature has not selected. An important application of this technology is the...
Enzymatic properties of rat DNA polymerase β mutants obtained by randomized mutagenesis
Skandalis, Adonis, Loeb, Lawrence A.
We have used random sequence mutagenesis to generate mutants of DNA polymerase β in an effort to identify amino acid residues important for function, catalytic efficiency and fidelity of...
Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA
Shen, Jiang-Cheng, Loeb, Lawrence A.
Werner syndrome (WS) is an autosomal recessive disease characterized by early onset of many features of aging, by an unusual spectrum of cancers, and by genomic instability. The WS protein (WRN)...
Mutations in human DNA polymerase η motif II alter bypass of DNA lesions
Glick, Eitan, Vigna, Kellie L., Loeb, Lawrence A.
Human DNA polymerase η (hPolη) is one of the newly identified Y-family of DNA polymerases. These polymerases synthesize past template lesions that are postulated to block replication fork...
Davidson, John F., Fox, Richard, Harris, Dawn D., Lyons-Abbott, Sally, Loeb, Lawrence A.
Insertion of the T3 DNA polymerase thioredoxin binding domain (TBD) into the distantly related thermostable Taq DNA polymerase at an analogous position in the thumb domain, converts the Taq DNA...
Targeted gene evolution in Escherichia coli using a highly error-prone DNA polymerase I
Camps, Manel, Naukkarinen, Jussi, Johnson, Ben P., Loeb, Lawrence A.
We present a system for random mutagenesis in Escherichia coli for the evolution of targeted genes. To increase error rates of DNA polymerase I (Pol I) replication, we introduced point mutations in...
Tumbling down a different pathway to genetic instability
Guo, Haiwei H., Loeb, Lawrence A.
Ulcerative colitis (UC), a chronic inflammatory condition associated with a predisposition to colon cancer, is frequently characterized by DNA damage in the form of microsatellite instability (MSI)....
Loeb, Lawrence A., Loeb, Keith R., Anderson, Jon P.
Most human tumors are highly heterogenous. We have hypothesized that this heterogeneity results from a mutator phenotype. Our premise is that normal mutation rates are insufficient to account for the...
DNA polymerase activity as an index of lymphocyte stimulation: studies in Down's syndrome
Agarwal, S. S., Blumberg, Baruch S., Gerstley, Betty Jane S., London, W. Thomas, Sutnick, Alton I., Loeb, Lawrence A.
The ability of peripheral blood lymphocytes to respond to phytohemagglutinin (PHA) in vitro was studied in patients with Down's syndrome. The response was measured by the increase in DNA polymerase...
Mutagenic DNA Polymerase in Human Leukemic Cells
Springgate, Clark F., Loeb, Lawrence A.
Evidence is presented that DNA polymerases from human leukemic cells are mutagenic. Nucleic acid-free extracts of acute lymphoblastic leukemic cells polymerized about 10-times more dCTP using...
Reverse Transcriptase: Correlation of Zinc Content with Activity
Poiesz, Bernard J., Seal, Gita, Loeb, Lawrence A.
Evidence is presented that DNA polymerase of avian myeloblastosis virus has an obligatory zinc requirement for activity. Previous studies indicate that the purified polymerase contains zinc in a...
Protein tolerance to random amino acid change
Guo, Haiwei H., Choe, Juno, Loeb, Lawrence A.
Mutagenesis of protein-encoding sequences occurs ubiquitously; it enables evolution, accumulates during aging, and is associated with disease. Many biotechnological methods exploit random mutations...
Khateb, Samer, Weisman-Shomer, Pnina, Hershco, Inbal, Loeb, Lawrence A., Fry, Michael
Hairpin or tetrahelical structures formed by a d(CGG)n sequence in the FMR1 gene are thought to promote expansion of the repeat tract. Subsequent to this expansion FMR1 is silenced and fragile X...
Negative Clonal Selection in Tumor Evolution
Beckman, Robert A., Loeb, Lawrence A.
Development of cancer requires the acquisition of multiple oncogenic mutations and selection of the malignant clone. Cancer evolves within a finite host lifetime and mechanisms of carcinogenesis that...
Efficiency of carcinogenesis with and without a mutator mutation
Beckman, Robert A., Loeb, Lawrence A.
Carcinogenesis involves the acquisition of multiple genetic changes altering various cellular phenotypes. These changes occur within the fixed time period of a human lifespan, and mechanisms that...
Human cancers express a mutator phenotype
Bielas, Jason H., Loeb, Keith R., Rubin, Brian P., True, Lawrence D., Loeb, Lawrence A.
Cancer cells contain numerous clonal mutations, i.e., mutations that are present in most or all malignant cells of a tumor and have presumably been selected because they confer a proliferative...
Werner syndrome protein interacts functionally with translesion DNA polymerases
Kamath-Loeb, Ashwini S., Lan, Li, Nakajima, Satoshi, Yasui, Akira, Loeb, Lawrence A.
Werner syndrome (WS) is characterized by premature onset of age-associated disorders and predisposition to cancer. The WS protein, WRN, encodes 3′ → 5′ DNA helicase and 3′ → 5′ DNA...
Venkatesan, Ranga N., Treuting, Piper M., Fuller, Evan D., Goldsby, Robert E., Norwood, Thomas H., Gooley, Ted A., ...
Mammalian DNA polymerase δ (Pol δ) is believed to replicate a large portion of the genome and to synthesize DNA in DNA repair and genetic recombination pathways. The effects of mutation in the...
AUSTRALIA ANTIGEN (A HEPATITIS-ASSOCIATED ANTIGEN) : PURIFICATION AND PHYSICAL PROPERTIES
Millman, Irving, Loeb, Lawrence A., Bayer, Manfred E., Blumberg, Baruch S.
Australia antigen [Au(1)], a particle associated with viral hepatitis, was isolated from the plasma of a patient with chronic anicteric hepatitis and leukemia who had received radioactive phosphorus....
ZINC REQUIREMENT FOR DNA REPLICATION IN STIMULATED HUMAN LYMPHOCYTES
Williams, Richard O., Loeb, Lawrence A.
The requirement for Zn++ in DNA replication by phytohemagglutinin-stimulated human lymphocytes was studied. When 6 µM o-phenanthroline, a chelator with a high affinity for Zn++, is added to cultures...