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Full-Text Articles in Life Sciences

Dna Damage Responses In Progeroid Syndromes Arise From Defective Maturation Of Prelamin A, Michael Sinensky, Y. Liu, A. Rusinol, Y. Wang, Y. Zou Jan 2006

Dna Damage Responses In Progeroid Syndromes Arise From Defective Maturation Of Prelamin A, Michael Sinensky, Y. Liu, A. Rusinol, Y. Wang, Y. Zou

Michael Sinensky

The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their ...


Analyzing Dna Microarrays With Undergraduate Statisticians, Johanna S. Hardin, Laura Hoopes, Ryan Murphy '06 Jan 2006

Analyzing Dna Microarrays With Undergraduate Statisticians, Johanna S. Hardin, Laura Hoopes, Ryan Murphy '06

Pomona Faculty Publications and Research

With advances in technology, biologists have been saddled with high dimensional data that need modern statistical methodology for analysis. DNA microarrays are able to simultaneously measure thousands of genes (and the activity of those genes) in a single sample. Biologists use microarrays to trace connections between pathways or to identify all genes that respond to a signal. The statistical tools we usually teach our undergraduates are inadequate for analyzing thousands of measurements on tens of samples. The project materials include readings on microarrays as well as computer lab activities. The topics covered include image analysis, filtering and normalization techniques, and ...


Polyamide Platinum Anti-Cancer Complexes Designed To Target Specific Dna Sequences, David Jaramillo, Nial J. Wheate, Stephen F. Ralph, Warren A. Howard, Yitzhak Tor, Janice Aldrich-Wright Jan 2006

Polyamide Platinum Anti-Cancer Complexes Designed To Target Specific Dna Sequences, David Jaramillo, Nial J. Wheate, Stephen F. Ralph, Warren A. Howard, Yitzhak Tor, Janice Aldrich-Wright

Faculty of Science - Papers (Archive)

Two new platinum complexes, trans-chlorodiammine[N-(2-aminoethyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-2) and trans-chlorodiammine[N-(6-aminohexyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-6) have been synthesized as proof-of-concept molecules in the design of agents that can specifically target genes in DNA. Coordinate covalent binding to DNA was demonstrated with electrospray ionization mass spectrometry. Using circular dichroism, these complexes were found to show greater DNA binding affinity to the target sequence:‚ÄČ d(CATTGTCAGAC)2, than toward either d(GTCTGTCAATG)2, which contains different flanking sequences, or d(CATTGAGAGAC)2, which contains a double base pair ...


Proteomic Dissection Of Dna Polymerization, Jennifer L. Beck, Thitima Urathamakul, Stephen James Watt, Margaret Sheil, Patrick M. Schaeffer, Nicholas E. Dixon Jan 2006

Proteomic Dissection Of Dna Polymerization, Jennifer L. Beck, Thitima Urathamakul, Stephen James Watt, Margaret Sheil, Patrick M. Schaeffer, Nicholas E. Dixon

Faculty of Science - Papers (Archive)

DNA polymerases replicate the genome by associating with a range of other proteins that enable rapid, high-fidelity copying of DNA. This complex of proteins and nucleic acids is called the replisome. Proteins of the replisome must interact with other networks of proteins, such as those involved in DNA repair. Many of the proteins involved in DNA polymerisation and the accessory proteins are known, but the array of proteins they interact with, and the spatial and temporal arrangement of these interactions is a current research topic. Mass spectrometry is a technique that can be used to identify the sites of these ...


Dna Damage Responses In Progeroid Syndromes Arise From Defective Maturation Of Prelamin A, Michael Sinensky, Y. Liu, A. Rusinol, Y. Wang, Y. Zou Jan 2006

Dna Damage Responses In Progeroid Syndromes Arise From Defective Maturation Of Prelamin A, Michael Sinensky, Y. Liu, A. Rusinol, Y. Wang, Y. Zou

Faculty Publications

The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their ...