HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE
BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN

D 2018

HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN

HOFR, Ctirad; Ivona NEČASOVÁ; Eliška JANOUŠKOVÁ; Tomáš JANOVIČ; Martin STOJASPAL et. al.

Základní údaje

Originální název

HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN

Autoři

HOFR, Ctirad (203 Česká republika, domácí); Ivona NEČASOVÁ (203 Česká republika, domácí); Eliška JANOUŠKOVÁ (203 Česká republika, domácí); Tomáš JANOVIČ (203 Česká republika, domácí); Martin STOJASPAL (203 Česká republika, domácí) a Pavel VEVERKA (203 Česká republika, domácí)

Vydání

Česká republika, 15 th International Interdisciplinary Meeting on Bioanalysis - Conference Proceedings, od s. 59-63, 5 s. 2018

Nakladatel

Institute of Analytical Chemistry of the CAS, v. v. i., Brno, Czech Republic

Další údaje

Jazyk

angličtina

Typ výsledku

Stať ve sborníku

Obor

10403 Physical chemistry

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Forma vydání

elektronická verze "online"

Odkazy

URL

Kód RIV

RIV/00216224:14740/18:00101393

Organizační jednotka

Středoevropský technologický institut

ISBN

978-80-904959-7-5

Klíčová slova anglicky

Telomere; SHELTERIN

Štítky

rivok

Změněno: 11. 3. 2019 12:51, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Telomere maintenance is a highly coordinated process that controls cell aging. Misregulation of telomere maintenance is linked to cancer and telomere-shortening syndromes. Recent studies have shown that the TEL-patch is a cluster of amino acids onthe surface of the shelterin component TPP1 that is essential for the recruitment of telomerase to the telomere in human cells. The Cech laboratory (Colorado University Boulder) and our laboratory (Masaryk University) optimized an in vitro assay to quantitatively measure binding of the TEL-patch to telomerase and extension of the first telomeric repeat. We quantified how the TEL-patch contributes to the translocation and stabilizes the association between telomerase and telomeric DNA substrates, providing a molecular explanation for its contributions to telomerase recruitment and action. Additionally, we quantitatively described interactions of TRF2 - central shelterin subunit that folds human telomeres into loops to prevent unwanted DNA repair and chromosome end joining. We found that the basic B-domain of TRF2 stabilizes the displacement loop (D-loop) and thus reduces unwinding by RPA and BLM helicase, whereas the formation of the RAP1–TRF2 complex restores DNA unwinding. To understand how the B-domain of TRF2 affects DNA binding and D-loop processing, we analyzed DNA binding of full-length TRF2 and a truncated TRF2 construct lacking the B-domain. We found that the Bdomain improves TRF2’s binding to DNA via enhanced long-range electrostatic interactions. We determined a structural envelope model revealing that the B-domain is flexible in solution but becomes rigid upon binding to telomeric DNA. We propose a mechanism for how the Bdomain stabilizes the D-loop and contributes to improved DNA affinity of TRF2 in general. Additionally, we suggest how human RAP1 regulates TRF2 attraction and specificity to DNA and thus degree of telomere protection by shelterin.

Návaznosti

GA16-20255S, projekt VaV

Název: Molekulární mechanismus inhibice telomerázy: cílené zastavení dělení nádorových buněk

Investor: Grantová agentura ČR, Molekulární mechanismus inhibice telomerázy: cílené zastavení dělení nádorových buněk

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

HOFR, Ctirad; Ivona NEČASOVÁ; Eliška JANOUŠKOVÁ; Tomáš JANOVIČ; Martin STOJASPAL a Pavel VEVERKA. HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN. Online. In František Foret, Jana Křenková, Iveta Drobníková, Karel Klepárník, Jan Přikryl. 15 th International Interdisciplinary Meeting on Bioanalysis - Conference Proceedings. Česká republika: Institute of Analytical Chemistry of the CAS, v. v. i., Brno, Czech Republic, 2018, s. 59-63. ISBN 978-80-904959-7-5.

@inproceedings{1474577,
   author = {Hofr, Ctirad and Nečasová, Ivona and Janoušková, Eliška and Janovič, Tomáš and Stojaspal, Martin and Veverka, Pavel},
   address = {Česká republika},
   booktitle = {15 th International Interdisciplinary Meeting on Bioanalysis - Conference Proceedings},
   editor = {František Foret, Jana Křenková, Iveta Drobníková, Karel Klepárník, Jan Přikryl},
   keywords = {Telomere; SHELTERIN},
   howpublished = {elektronická verze "online"},
   language = {eng},
   location = {Česká republika},
   isbn = {978-80-904959-7-5},
   pages = {59-63},
   publisher = {Institute of Analytical Chemistry of the CAS, v. v. i., Brno, Czech Republic},
   title = {HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN},
   url = {http://www.ce-ce.org},
   year = {2018}
}

TY  - CONF
ID  - 1474577
AU  - Hofr, Ctirad - Nečasová, Ivona - Janoušková, Eliška - Janovič, Tomáš - Stojaspal, Martin - Veverka, Pavel
PY  - 2018
TI  - HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN
PB  - Institute of Analytical Chemistry of the CAS, v. v. i., Brno, Czech Republic
CY  - Česká republika
SN  - 9788090495975
KW  - Telomere
KW  - SHELTERIN
UR  - http://www.ce-ce.org
N2  - Telomere maintenance is a highly coordinated process that controls cell aging. Misregulation of telomere maintenance is linked to cancer and telomere-shortening syndromes. Recent studies have shown that the TEL-patch is a cluster of amino acids onthe surface of the shelterin component TPP1 that is essential for the recruitment of telomerase to the telomere in human cells. The Cech laboratory (Colorado University Boulder) and our laboratory (Masaryk University) optimized an in vitro assay to quantitatively measure binding of the TEL-patch to telomerase and extension of the first telomeric repeat. We quantified how the TEL-patch contributes to the translocation and stabilizes the association between telomerase and telomeric DNA substrates, providing a molecular explanation for its contributions to telomerase recruitment and action. Additionally, we quantitatively described interactions of TRF2 - central shelterin subunit that folds human telomeres into loops to prevent unwanted DNA repair and chromosome end joining. We found that the basic B-domain of TRF2 stabilizes the displacement loop (D-loop) and thus reduces unwinding by RPA and BLM helicase, whereas the formation of the RAP1–TRF2 complex restores DNA unwinding. To understand how the B-domain of TRF2 affects DNA binding and D-loop processing, we analyzed DNA binding of full-length TRF2 and a truncated TRF2 construct lacking the B-domain. We found that the Bdomain improves TRF2’s binding to DNA via enhanced long-range electrostatic interactions. We determined a structural envelope model revealing that the B-domain is flexible in solution but becomes rigid upon binding to telomeric DNA. We propose a mechanism for how the Bdomain stabilizes the D-loop and contributes to improved DNA affinity of TRF2 in general. Additionally, we suggest how human RAP1 regulates TRF2 attraction and specificity to DNA and thus degree of telomere protection by shelterin.
ER  -

HOFR, Ctirad; Ivona NEČASOVÁ; Eliška JANOUŠKOVÁ; Tomáš JANOVIČ; Martin STOJASPAL a Pavel VEVERKA. HOW TO TRAIN OUR CELLS TO BECOME YOUNGER – QUANTITATIVE BIOPHYSICS OF HUMAN TELOMERASE AND ITS GUARD SHELTERIN. Online. In František Foret, Jana Křenková, Iveta Drobníková, Karel Klepárník, Jan Přikryl. \textit{15 th International Interdisciplinary Meeting on Bioanalysis - Conference Proceedings}. Česká republika: Institute of Analytical Chemistry of the CAS, v. v. i., Brno, Czech Republic, 2018, s.~59-63. ISBN~978-80-904959-7-5.

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