Medical News Today , Article Date: 15 Jul 2009 - 0:00 PDT
Researchers at the University of Kentucky Markey Cancer Center and Graduate Center for Toxicology (GCT) have gained new insight into the genetic mechanisms underlying Huntington's disease and other neurodegenerative or neuromuscular disorders caused by trinucleotide repeats (or TNRs) in DNA.
This newspaper article is based on this research: http://friedreichscientificnews.blogspot.com/2009/07/incision-dependent-and-error-free.html
Wednesday, July 15, 2009
Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts
Nat Struct Mol Biol. 2009 Jul 13
Hou C, Chan NL, Gu L, Li GM.
Graduate Center for Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Keywords: Expansion of CAG/CTG trinucleotide repeats, neurological disorders, Huntington's disease, proliferating cell nuclear antigen (PCNA), endonuclease activities, trinucleotide repeat instability.
Hou C, Chan NL, Gu L, Li GM.
Graduate Center for Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Keywords: Expansion of CAG/CTG trinucleotide repeats, neurological disorders, Huntington's disease, proliferating cell nuclear antigen (PCNA), endonuclease activities, trinucleotide repeat instability.
[Diseases caused by triplet expansion.]
Rev Neurol. 2009 Jul 16-31;49(2):79-87
[Article in Spanish]
Rosales-Reynoso MA, Ochoa-Hernandez AB, Barros-Nunez P.
Centro de Investigacion Biomedica de Occidente IMSS (CIBO), Guadalajara, Mexico
Keywords: expansion of nucleotide triplets, meiosis, mitosis, CGG/ GCC, CAG/GTC, CTG/GAC, GAA/CTT, bulbospinal muscular atrophy, Huntington's diseas, spinocerebellar ataxias, fragile X syndrome, Friedreich's ataxia, myotonic dystrophy, cis-acting, trans-acting, pre-mutations, dynamic mutation processes.
[Article in Spanish]
Rosales-Reynoso MA, Ochoa-Hernandez AB, Barros-Nunez P.
Centro de Investigacion Biomedica de Occidente IMSS (CIBO), Guadalajara, Mexico
Keywords: expansion of nucleotide triplets, meiosis, mitosis, CGG/ GCC, CAG/GTC, CTG/GAC, GAA/CTT, bulbospinal muscular atrophy, Huntington's diseas, spinocerebellar ataxias, fragile X syndrome, Friedreich's ataxia, myotonic dystrophy, cis-acting, trans-acting, pre-mutations, dynamic mutation processes.
Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy
OPEN ACCES
Min-Suk Yoon , Zaza Katsarava , Mark Obermann , Maria Schaefers , Bernd Liedert , Anna Dzagnidze , Andreas Kribben , Rupert Egensperger , Volker Limmroth , Hans Christoph-Diener and Juergen Thomale
BMC Neuroscience 2009, 10:77doi:10.1186/1471-2202-10-77
Published:
15 July 2009
Abstract (provisional)
Background
Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO) protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden.
Results
A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s +/- 1,68 m/s; cisplatin + rhEPO 49,66 m/s +/- 1,26 m/s; control 55,01 m/s +/- 1,88 m/s; p < 0,001). The co-application of rhEPO, however, did not alter the level of unrepaired cisplatin-DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural injuries and resulted in an increased number of intact mitochondria.
Conclusion
The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.
Full text: http://www.biomedcentral.com/content/pdf/1471-2202-10-77.pdf
Min-Suk Yoon , Zaza Katsarava , Mark Obermann , Maria Schaefers , Bernd Liedert , Anna Dzagnidze , Andreas Kribben , Rupert Egensperger , Volker Limmroth , Hans Christoph-Diener and Juergen Thomale
BMC Neuroscience 2009, 10:77doi:10.1186/1471-2202-10-77
Published:
15 July 2009
Abstract (provisional)
Background
Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO) protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden.
Results
A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s +/- 1,68 m/s; cisplatin + rhEPO 49,66 m/s +/- 1,26 m/s; control 55,01 m/s +/- 1,88 m/s; p < 0,001). The co-application of rhEPO, however, did not alter the level of unrepaired cisplatin-DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural injuries and resulted in an increased number of intact mitochondria.
Conclusion
The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.
Full text: http://www.biomedcentral.com/content/pdf/1471-2202-10-77.pdf
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