Human Rap1 modulates TRF2 attraction to telomeric DNA

J 2015

Human Rap1 modulates TRF2 attraction to telomeric DNA

JANOUŠKOVÁ, Eliška; Ivona NEČASOVÁ; Jana PAVLOUŠKOVÁ; Michal ZIMMERMANN; Milan HLUCHÝ et al.

Základní údaje

Originální název

Human Rap1 modulates TRF2 attraction to telomeric DNA

Autoři

JANOUŠKOVÁ, Eliška; Ivona NEČASOVÁ; Jana PAVLOUŠKOVÁ; Michal ZIMMERMANN; Milan HLUCHÝ; María Victoria MARINI PALOMEQUE; Monika NOVÁKOVÁ a Ctirad HOFR

Vydání

Nucleic Acids Research, Oxford, Oxford University Press, 2015, 0305-1048

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.202

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/15:00081706

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

MAMMALIAN TELOMERES; HOLLIDAY JUNCTIONS; PROTEIN; PROTECTION; SHELTERIN; BINDING; LOOP; END; ATM; RECRUITMENT

Štítky

podil, rivok

Změněno: 21. 4. 2016 13:15, Mgr. Eva Špillingová

Anotace

V originále

More than two decades of genetic research have identified and assigned main biological functions of shelterin proteins that safeguard telomeres. However, a molecular mechanism of how each protein subunit contributes to the protecting function of the whole shelterin complex remains elusive. Human Repressor activator protein 1 (Rap1) forms a multifunctional complex with Telomeric Repeat binding Factor 2 (TRF2). Rap1-TRF2 complex is a critical part of shelterin as it suppresses homology-directed repair in Ku 70/80 heterodimer absence. To understand how Rap1 affects key functions of TRF2, we investigated full-length Rap1 binding to TRF2 and Rap1-TRF2 complex interactions with double-stranded DNA by quantitative biochemical approaches. We observed that Rap1 reduces the overall DNA duplex binding affinity of TRF2 but increases the selectivity of TRF2 to telomeric DNA. Additionally, we observed that Rap1 induces a partial release of TRF2 from DNA duplex. The improved TRF2 selectivity to telomeric DNA is caused by less pronounced electrostatic attractions between TRF2 and DNA in Rap1 presence. Thus, Rap1 prompts more accurate and selective TRF2 recognition of telomeric DNA and TRF2 localization on single/double-strand DNA junctions. These quantitative functional studies contribute to the understanding of the selective recognition of telomeric DNA by the whole shelterin complex.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

GAP205/12/0550, projekt VaV

Název: Dynamika vzniku shelterinového komplexu

Investor: Grantová agentura ČR, Dynamika vzniku shelterinového komplexu

GAP207/12/2323, projekt VaV

Název: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Grantová agentura ČR, Endonuleázová a translokázová aktivita v restrikčních-modifikačních komplexech typu I

GA13-26693S, projekt VaV

Název: Genetická diverzita a fylogeneze rodu Acinetobacter v přírodních ekosystémech.

Investor: Grantová agentura ČR, Genetická diverzita a fylogeneze rodu Acinetobacter v přírodních ekosystémech

LH13054, projekt VaV

Název: Studium dynamiky telomerových proteinových komplexů zajišťujících stabilitu genomu (Akronym: TeloProtGen)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Studium dynamiky telomerových proteinových komplexů zajišťujících stabilitu genomu

Přiložené soubory

EL_1342280.pdf

Požádat o autorskou verzi souboru

Citovat

JANOUŠKOVÁ, Eliška; Ivona NEČASOVÁ; Jana PAVLOUŠKOVÁ; Michal ZIMMERMANN; Milan HLUCHÝ; María Victoria MARINI PALOMEQUE; Monika NOVÁKOVÁ a Ctirad HOFR. Human Rap1 modulates TRF2 attraction to telomeric DNA. Nucleic Acids Research. Oxford: Oxford University Press, 2015, roč. 43, č. 5, s. 2691-2700. ISSN 0305-1048. Dostupné z: https://doi.org/10.1093/nar/gkv097.

@article{1342280,
   author = {Janoušková, Eliška and Nečasová, Ivona and Pavloušková, Jana and Zimmermann, Michal and Hluchý, Milan and Marini Palomeque, María Victoria and Nováková, Monika and Hofr, Ctirad},
   article_location = {Oxford},
   article_number = {5},
   doi = {https://doi.org/10.1093/nar/gkv097},
   keywords = {MAMMALIAN TELOMERES; HOLLIDAY JUNCTIONS; PROTEIN; PROTECTION; SHELTERIN; BINDING; LOOP; END; ATM; RECRUITMENT},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Human Rap1 modulates TRF2 attraction to telomeric DNA},
   url = {http://nar.oxfordjournals.org/content/43/5/2691.full.pdf+html},
   volume = {43},
   year = {2015}
}

TY  - JOUR
ID  - 1342280
AU  - Janoušková, Eliška - Nečasová, Ivona - Pavloušková, Jana - Zimmermann, Michal - Hluchý, Milan - Marini Palomeque, María Victoria - Nováková, Monika - Hofr, Ctirad
PY  - 2015
TI  - Human Rap1 modulates TRF2 attraction to telomeric DNA
JF  - Nucleic Acids Research
VL  - 43
IS  - 5
SP  - 2691-2700
EP  - 2691-2700
PB  - Oxford University Press
SN  - 03051048
KW  - MAMMALIAN TELOMERES
KW  - HOLLIDAY JUNCTIONS
KW  - PROTEIN
KW  - PROTECTION
KW  - SHELTERIN
KW  - BINDING
KW  - LOOP
KW  - END
KW  - ATM
KW  - RECRUITMENT
UR  - http://nar.oxfordjournals.org/content/43/5/2691.full.pdf+html
L2  - http://nar.oxfordjournals.org/content/43/5/2691.full.pdf+html
N2  - More than two decades of genetic research have identified and assigned main biological functions of shelterin proteins that safeguard telomeres. However, a molecular mechanism of how each protein subunit contributes to the protecting function of the whole shelterin complex remains elusive. Human Repressor activator protein 1 (Rap1) forms a multifunctional complex with Telomeric Repeat binding Factor 2 (TRF2). Rap1-TRF2 complex is a critical part of shelterin as it suppresses homology-directed repair in Ku 70/80 heterodimer absence. To understand how Rap1 affects key functions of TRF2, we investigated full-length Rap1 binding to TRF2 and Rap1-TRF2 complex interactions with double-stranded DNA by quantitative biochemical approaches. We observed that Rap1 reduces the overall DNA duplex binding affinity of TRF2 but increases the selectivity of TRF2 to telomeric DNA. Additionally, we observed that Rap1 induces a partial release of TRF2 from DNA duplex. The improved TRF2 selectivity to telomeric DNA is caused by less pronounced electrostatic attractions between TRF2 and DNA in Rap1 presence. Thus, Rap1 prompts more accurate and selective TRF2 recognition of telomeric DNA and TRF2 localization on single/double-strand DNA junctions. These quantitative functional studies contribute to the understanding of the selective recognition of telomeric DNA by the whole shelterin complex.
ER  -

JANOUŠKOVÁ, Eliška; Ivona NEČASOVÁ; Jana PAVLOUŠKOVÁ; Michal ZIMMERMANN; Milan HLUCHÝ; María Victoria MARINI PALOMEQUE; Monika NOVÁKOVÁ a Ctirad HOFR. Human Rap1 modulates TRF2 attraction to telomeric DNA. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2015, roč.~43, č.~5, s.~2691-2700. ISSN~0305-1048. Dostupné z: https://doi.org/10.1093/nar/gkv097.

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