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TRISCPOL SIGNED

The role of the iron-sulpur cluster in human DNA polymerase delta

Total Cost €

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EC-Contrib. €

0

Partnership

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 TRISCPOL project word cloud

Explore the words cloud of the TRISCPOL project. It provides you a very rough idea of what is the project "TRISCPOL" about.

functionally    vivo    hydrogen    deuterium    genome    astonishing    demonstrated    cluster    stability    functional    fidelity    assays    mutants    molecular    function    transport    mass    metabolism    resonance    ageing    replicative    respiratory    remained    polymerase    employed    clusters    discovered    basis    characterise    electron    eukaryotic    exchange    iron    fes    binding    polymerases    premature    depleted    treatment    yeast    sulphur    elusive    techniques    spectrometry    light    co    ancient    processivity    cell    engineered    hence    prior    shed    region    unveiling    visible    mitochondrial    pol    uv    triscpol    dna    spectroscopy    proteins    endogenous    delta    largely    surprising    division    confirm    incorporation    stress    versatile    tested    synthesis    measured    paramagnetic    structural    actual    combination    replicases    replicated    vitro    subjected    complement    chain    oxidative    contain    requirement    strategies    cancer    enzymes    accuracy    cells    replication    pairs    base    billion    human    purified   

Project "TRISCPOL" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT ZURICH 

Organization address
address: RAMISTRASSE 71
city: Zürich
postcode: 8006
website: http://www.unizh.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Project website https://www.researchgate.net/profile/Stanislaw_Jozwiakowski
 Total cost 187˙419 €
 EC max contribution 187˙419 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2018-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT ZURICH CH (Zürich) coordinator 187˙419.00

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 Project objective

The human genome is composed of 3 billion base pairs of DNA that are replicated prior to every cell division with an astonishing accuracy. High-fidelity replication is necessary to maintain genome stability, and hence to avoid premature ageing and cancer. This project aims at understanding the role of the iron-sulphur (FeS) cluster in human DNA polymerase delta (Pol δ), one of the major replicases. FeS clusters are ancient and versatile co-factors that are commonly known for their function in electron transport in the mitochondrial respiratory chain. In recent years, a surprising number of proteins involved in DNA metabolism have been discovered to contain an FeS cluster including all replicative DNA polymerases in yeast. While the requirement of an FeS cluster for the function of replicases was demonstrated, the actual role of the FeS cluster in these enzymes has remained largely elusive. The TRISCPOL project aims to: 1) Confirm and characterise the FeS cluster in human Pol δ by using iron incorporation assays, UV-visible and electron paramagnetic resonance spectroscopy. 2) Determine the role of the FeS cluster in human Pol δ in vitro. Purified Pol δ will be subjected to oxidative stress conditions, and then changes in structural and functional features will be measured. A combination of techniques including deuterium-hydrogen exchange mass spectrometry, as well as DNA binding, DNA synthesis, processivity and fidelity assays, will be employed. 3) Define the role of the FeS cluster in human Pol δ in vivo. Mutants in the FeS cluster-binding region will be engineered and tested for their ability to functionally complement cells depleted of endogenous Pol δ. Unveiling the role of the FeS cluster in human Pol δ will shed new light on the principle of eukaryotic DNA replication. Moreover, this knowledge will contribute to our understanding of the molecular basis of cancer and may eventually allow the development of novel strategies of treatment.

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The information about "TRISCPOL" are provided by the European Opendata Portal: CORDIS opendata.

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