histonas y telomerasas
TRANSCRIPT
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Telomeros
Universidad de Caldas Biología Molecular
Walter Ricardo López
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Albrecht Kossel (1853-‐1927) Nobel 1910 ( descripción del núcleo celular) Aisló y describió: • Guanina • Adenina • Citosina • Uracilo • Timina
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Histonas
• Son proteínas cargadas posiSvamente (lisina y arginina) • Forman los nucleosomas • Agrupan el ADN • Existen 5 Spos ü Centro; H2A, H2B, H3, H4 ü Unión: H1
h[p://www.fastbleep.com/biology-‐notes/40/116/1191
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h[p://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-‐18/18_21.jpg
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147pb en protozoos son agrupadas por las histonas 2000pb en levaduras
Ransom et al., 2010 Sauerwald et al., 2013
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h[p://www.mun.ca/biology/desmid/brian/BIOL2060/BIOL2060-‐18/18_18.jpg
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Niveles de empaquetamiento del ADN
1. Nucleosoma 2. CromaSna/Solenoides 3. Dominios de orquillas 4. Cromosomas
h[p://www.oryzon.com/en/drug-‐discovery
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h[p://www.gistsupport.org/learning-‐center/cells-‐cancer-‐and-‐more/how-‐dna-‐is-‐packaged-‐in-‐a-‐cell.php
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Final de la replicación?
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Telomeros
• Son secuencias de ADN no codificante • Se encuentran al final de los cromosomas • Proporcionan estabilidad cromosomal • Están consStuidos por subunidades cortas (TTAGGG) • Disminución de la estructura telomerica contribuye a la inestabilidad
genómica • Definen la vida de la célula
h[p://telomerase.asu.edu/sequences.html
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Telomerasa
• Fue descubierta en 1984 por Carol W Grieider y Elizabeth Blackburn • Tetrahymena thermophila • Es una ribonucleoproteina • Adiciona secuencias TTAGGG al extremo 3’ • La telomerasa humana es una transcriptasa reversa • Presenta una subunidad de RNA TER • Presenta una subunidad proteica TERT con tres dominios: ü N terminal de union a G (TEN) ü Un dominio de union a RNA (TRBD) ü Un dominio C terminal trasciptasa reversa (RTD) • En células normales su acSvidad es baja o casi nula • En células cancerosas su acSvidad puede ser muy alta
Sauerwald et al., 2013 www.cadaster.eu
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www.nobelprize.org
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Harley ., 2008.
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h[p://www.grenswetenschap.nl/permalink.asp?grens=2457
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(g,h) Electron micrographs of telomerase bound by 5-‐nm colloidal gold coated with streptavidin in the presence (g) and absence (h) of telomerase. Circles denote telomerase dimers in complex with one gold parScle (red) or two gold parScles (yellow). Arrows indicate colloidal gold parScles that are not bound to telomerase. Scale bars, 50 nm (d,g,h)
Sauerwald et al., 2013
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Sauerwald et al., 2013
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Alabert C, 2012.
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Alabert C, 2012.
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REFERENCIAS
Alabert C, Groth A. ChromaSn replicaSon and epigenome maintenance. Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):153-‐67. Harley CB. Telomerase and cancer therapeuScs. Nat Rev Cancer. 2008 Mar;8(3):167-‐79 Ransom M , Dennehey B. K, Tyler J. K. Chaperoning Histones during DNA ReplicaSon and Repair. Cell -‐ 22 January 2010 .Vol. 140, Issue 2, pp. 183-‐195. Sauerwald A, Sandin S, Cristofari G, Scheres SH, Lingner J, Rhodes D. Structure of acSve dimeric human telomerase. Nat Struct Mol Biol. 2013 Apr;20(4):454-‐60