Summary
Background and unmet need:
The mammalian genome is a highly organized structure where distinct
chromosomal domains occupy discrete territories and position in a non-random fashion. Genome
organization also determines the proper functioning of various biological processes, including DNA
replication. Genome organization has been widely studied in the context of gene regulation, while
recently the role of genome organization in mediating DNA damage repair at DSB sites has also come
to light. However, there is scarce information on how newly replicating region is organized in response
to replication stress.
Hypothesis to be tested:
My hypothesis is that stalled replication forks, especially at the regions prone
to acquire breaks, undergo compartmentalization/re-organization within the 3-D nuclear space in
response to replication stress to allow efficient fork protection and fork restart ability.
Objectives:
This unique multidisciplinary project will yield critical information to reveal hidden
connections of chromatin organization, replication fork stability and chemoresistance. With this ERC
project, I will determine for the first time i) the mechanistic insights of chromatin organization changes
mediated by chromatin remodeling activity in response to replication stress, ii) identify novel chromatin
mobilizers associated with replication forks and iii) determine the significance of chromatin reorganization
to cope with replication stress for establishing resistance towards chemotherapeutic drugs
in cancer cells and patient samples.
Expected Outcomes:
My project will not only advance our fundamental knowledge on spatial &
temporal reorganization of chromatin architecture containing stressed replication forks, but it also has a
high potential to contribute to identifying novel targets aimed at chromatin organizers that mediates
resistance towards replication stress inducing chemotherapeutics.
The mammalian genome is a highly organized structure where distinct
chromosomal domains occupy discrete territories and position in a non-random fashion. Genome
organization also determines the proper functioning of various biological processes, including DNA
replication. Genome organization has been widely studied in the context of gene regulation, while
recently the role of genome organization in mediating DNA damage repair at DSB sites has also come
to light. However, there is scarce information on how newly replicating region is organized in response
to replication stress.
Hypothesis to be tested:
My hypothesis is that stalled replication forks, especially at the regions prone
to acquire breaks, undergo compartmentalization/re-organization within the 3-D nuclear space in
response to replication stress to allow efficient fork protection and fork restart ability.
Objectives:
This unique multidisciplinary project will yield critical information to reveal hidden
connections of chromatin organization, replication fork stability and chemoresistance. With this ERC
project, I will determine for the first time i) the mechanistic insights of chromatin organization changes
mediated by chromatin remodeling activity in response to replication stress, ii) identify novel chromatin
mobilizers associated with replication forks and iii) determine the significance of chromatin reorganization
to cope with replication stress for establishing resistance towards chemotherapeutic drugs
in cancer cells and patient samples.
Expected Outcomes:
My project will not only advance our fundamental knowledge on spatial &
temporal reorganization of chromatin architecture containing stressed replication forks, but it also has a
high potential to contribute to identifying novel targets aimed at chromatin organizers that mediates
resistance towards replication stress inducing chemotherapeutics.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101078750 |
| Start date: | 01-03-2023 |
| End date: | 29-02-2028 |
| Total budget - Public funding: | 1 500 000,00 Euro - 1 500 000,00 Euro |
Cordis data
Original description
Background and unmet need:The mammalian genome is a highly organized structure where distinct
chromosomal domains occupy discrete territories and position in a non-random fashion. Genome
organization also determines the proper functioning of various biological processes, including DNA
replication. Genome organization has been widely studied in the context of gene regulation, while
recently the role of genome organization in mediating DNA damage repair at DSB sites has also come
to light. However, there is scarce information on how newly replicating region is organized in response
to replication stress.
Hypothesis to be tested:
My hypothesis is that stalled replication forks, especially at the regions prone
to acquire breaks, undergo compartmentalization/re-organization within the 3-D nuclear space in
response to replication stress to allow efficient fork protection and fork restart ability.
Objectives:
This unique multidisciplinary project will yield critical information to reveal hidden
connections of chromatin organization, replication fork stability and chemoresistance. With this ERC
project, I will determine for the first time i) the mechanistic insights of chromatin organization changes
mediated by chromatin remodeling activity in response to replication stress, ii) identify novel chromatin
mobilizers associated with replication forks and iii) determine the significance of chromatin reorganization
to cope with replication stress for establishing resistance towards chemotherapeutic drugs
in cancer cells and patient samples.
Expected Outcomes:
My project will not only advance our fundamental knowledge on spatial &
temporal reorganization of chromatin architecture containing stressed replication forks, but it also has a
high potential to contribute to identifying novel targets aimed at chromatin organizers that mediates
resistance towards replication stress inducing chemotherapeutics.
Status
SIGNEDCall topic
ERC-2022-STGUpdate Date
31-07-2023
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