Project #2535
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#2535 : Influence of chromatin dynamics on genomic stability during replication
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Name of Applicant : Luciana Lazar Stefanita
Date of application : 02-03-2015
Unit : Spatial Regulation of Genomes
Location : Jacob – 4 -
Phone : 9365
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Project context and summary :

Genomic DNA is hierarchically packed within the living cells and genome duplication requires the concerted effort of many thousands of individual replication units. As such, to ensure the integrity of transmission of the genetic information, both eukaryotes and prokaryotes have evolved sophisticated mechanisms to monitor DNA replication. Some of these mechanisms aim to maintain both a temporal and a spatial organization of the replication program, leading to multiple replication time regions and the compartmentalization into replication foci, subnuclear sites which accumulate numerous DNA replication factors. It should be noted that Saccharomyces cerevisiae represents an exception to the standard eukaryotic strategy for genome duplication. Similar to bacteria, S. cerevisiae possess well-defined replication origin sequences that can fire at a very efficient rate during S phase, leading to a very homogenous pattern of DNA replication. A common mo del suggests that, once replication starts dynamic events take place since co-regulated replication forks, having similar replication timing, cluster within a discrete number of foci that show distinct patterns of nuclear localization over the S-phase. Once initiated, the DNA synthesis might be compromised if the replication fork encounters an RFB (Replication Fork Barrier) such as DNA lesions, tightly bound protein-DNA complexes etc. The RFBs are considered a potential source of genetic instability and may lead to many chromosomal rearrangements. As a consequence, eukaryotes employ a complex DNA damage response against RFBs, which aims to maintain the stability of the stalled forks and provides the time required to repair and resume replication. Recent observations suggest that the non-random organization of the nucleus affects where repair occurs. The aim of this project is to reach a better understanding of the influence of the nuclear spatial architecture and organization at replication fork blocks.

Related team publications :
Marbouty, Marie-Nelly, Cournac, Flot, Mozziconacci, Koszul "meta3C unveils the diversity of chromosome organization in microorganisms" eLife, 2014
Marie-Nelly*, Marbouty, Cournac, Flot, Liti, Pande-Parodi, Syan, Guillen, Margeot, Zimmer*, Koszul "High-resolution genome (re)assembly using chromosome contact information" Nature Communications, 2014
Marie-Nelly, Marbouty, Cournac, Liti, Fischer, Zimmer, Koszul “Identifying functional elements in yeasts using genomewide contact maps" Bioinformatics, 2014
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Project Type : Medium
Status : Closed

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