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REPSUMODDT SIGNED

Mechanisms and regulators coordinating replication integrity and DNA damage tolerance.

Total Cost €

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EC-Contrib. €

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Partnership

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Project "REPSUMODDT" data sheet

The following table provides information about the project.

Coordinator
IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE 

Organization address
address: VIA ADAMELLO 16
city: MILANO
postcode: 20139
website: www.ifom-firc.it

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 Italy [IT]
 Total cost 1˙991˙250 €
 EC max contribution 1˙991˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE IT (MILANO) coordinator 1˙991˙250.00

Map

 Project objective

Accurate chromosomal DNA replication is of fundamental importance for cellular function, genome integrity and development. In response to replication perturbations, DNA damage response (DDR) and DNA damage tolerance (DDT) pathways become activated and are crucial for detection and tolerance of lesions, as well as for facilitating replication completion and supporting chromosome structural integrity. While important functions and key players of these regulatory processes have been outlined, much less is known about the choreography and mechanistic interplay between DDR and DDT during replication. Moreover, the principles by which they uniquely or commonly affect replication-associated chromosome integrity remain poorly understood. Here, we will use novel tools and a palette of ingenious genetic, molecular and proteomic based experimental strategies, to investigate the replication stress response triggered by diverse endogenous and exogenous cues, and to identify the underlying mechanisms. We will define the principles of local and temporal regulation of DDT in response to genotoxic stress, with a focus on the mechanisms of SUMO-regulated DNA metabolism processes. Additionally, we will investigate the topological DNA transitions triggered at intrinsically difficult to replicate genomic regions, stalled and terminal forks, with the aim of identifying key mechanisms and regulators of replication integrity at specific complex genomic regions or following specific types of replication stress. Finally, we will explore the relationship between DDT, replication fork architecture and sister chromatid cohesion in the context of DDR- and SUMO-orchestrated DNA transactions. We expect that these studies will reveal new aspects of how replication-associated DNA metabolism processes are inter-related and regulated, uniformly or at specific loci in the genome, and will break new ground in areas of replication mechanisms and chromosome integrity in general.

 Publications

year authors and title journal last update
List of publications.
2018 Maria G Iacovella, Michael Bremang, Omer Basha, Luciano Giacò, Walter Carotenuto, Cristina Golfieri, Barnabas Szakal, Marianna Dal Maschio, Valentina Infantino, Galina V Beznoussenko, Chinnu R Joseph, Clara Visintin, Alexander A Mironov, Rosella Visintin, Dana Branzei, Sébastien Ferreira-Cerca, Esti Yeger-Lotem, Peter De Wulf
Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae
published pages: 7586-7611, ISSN: 0305-1048, DOI: 10.1093/nar/gky618
Nucleic Acids Research 46/15 2019-06-18
2016 Dana Branzei, Andrea Ciliberto
Not all roads lead to Cdk1
published pages: 395-396, ISSN: 1538-4101, DOI: 10.1080/15384101.2016.1274585
Cell Cycle 16/5 2019-06-18
2018 Ireneusz Litwin, Tomasz Bakowski, Barnabas Szakal, Ewa Pilarczyk, Ewa Maciaszczyk‐Dziubinska, Dana Branzei, Robert Wysocki
Error‐free DNA damage tolerance pathway is facilitated by the Irc5 translocase through cohesin
published pages: e98732, ISSN: 0261-4189, DOI: 10.15252/embj.201798732
The EMBO Journal 37/18 2019-06-18
2017 Michele Giannattasio, Dana Branzei
S-phase checkpoint regulations that preserve replication and chromosome integrity upon dNTP depletion
published pages: 2361-2380, ISSN: 1420-682X, DOI: 10.1007/s00018-017-2474-4
Cellular and Molecular Life Sciences 74/13 2019-06-18
2018 Anjana Srivatsan, Bin-Zhong Li, Barnabas Szakal, Dana Branzei, Christopher D. Putnam, Richard D. Kolodner
The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06131-2
Nature Communications 9/1 2019-06-18
2018 Takuya Abe, Ryotaro Kawasumi, Michele Giannattasio, Sabrina Dusi, Yui Yoshimoto, Keiji Miyata, Koyuki Umemura, Kouji Hirota, Dana Branzei
AND-1 fork protection function prevents fork resection and is essential for proliferation
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05586-7
Nature Communications 9/1 2019-06-18
2017 Ryotaro Kawasumi, Takuya Abe, Hiroshi Arakawa, Massimiliano Garre, Kouji Hirota, Dana Branzei
ESCO1/2\'s roles in chromosome structure and interphase chromatin organization
published pages: 2136-2150, ISSN: 0890-9369, DOI: 10.1101/gad.306084.117
Genes & Development 31/21 2019-06-18
2017 Dana Branzei, Barnabas Szakal
Building up and breaking down: mechanisms controlling recombination during replication
published pages: 381-394, ISSN: 1040-9238, DOI: 10.1080/10409238.2017.1304355
Critical Reviews in Biochemistry and Molecular Biology 52/4 2019-06-18
2018 Takuya Abe, Masato Ooka, Ryotaro Kawasumi, Keiji Miyata, Minoru Takata, Kouji Hirota, Dana Branzei
Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites
published pages: 8412-8417, ISSN: 0027-8424, DOI: 10.1073/pnas.1803110115
Proceedings of the National Academy of Sciences 115/33 2019-06-18
2018 Takuya Abe, Masato Ooka, Ryotaro Kawasumi, Keiji Miyata, Minoru Takata, Kouji Hirota, Dana Branzei
Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites
published pages: 8412-8417, ISSN: 0027-8424, DOI: 10.1073/pnas.1803110115
Proceedings of the National Academy of Sciences 115/33 2019-05-09
2018 Anjana Srivatsan, Bin-Zhong Li, Barnabas Szakal, Dana Branzei, Christopher D. Putnam, Richard D. Kolodner
The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06131-2
Nature Communications 9/1 2019-05-09
2018 Maria G Iacovella, Michael Bremang, Omer Basha, Luciano Giacò, Walter Carotenuto, Cristina Golfieri, Barnabas Szakal, Marianna Dal Maschio, Valentina Infantino, Galina V Beznoussenko, Chinnu R Joseph, Clara Visintin, Alexander A Mironov, Rosella Visintin, Dana Branzei, Sébastien Ferreira-Cerca, Esti Yeger-Lotem, Peter De Wulf
Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae
published pages: 7586-7611, ISSN: 0305-1048, DOI: 10.1093/nar/gky618
Nucleic Acids Research 46/15 2019-05-09
2018 Ireneusz Litwin, Tomasz Bakowski, Barnabas Szakal, Ewa Pilarczyk, Ewa Maciaszczyk‐Dziubinska, Dana Branzei, Robert Wysocki
Error‐free DNA damage tolerance pathway is facilitated by the Irc5 translocase through cohesin
published pages: e98732, ISSN: 0261-4189, DOI: 10.15252/embj.201798732
The EMBO Journal 37/18 2019-05-09
2019 Michele Giannattasio, Dana Branzei
DNA Replication Through Strand Displacement During Lagging Strand DNA Synthesis in Saccharomyces cerevisiae
published pages: 167, ISSN: 2073-4425, DOI: 10.3390/genes10020167
Genes 10/2 2019-08-29

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