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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. €

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Partnership

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 Outcomes and results

 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.

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

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

Map

 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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