Doctoral thesis
English

Mechanisms underlying genomic instability in human cancers

ContributorsSotiriou, Sotirios
Defense date2016-01-28
Abstract

DNA replication is a very well orchestrated process that results in the accurate duplication of the genome. Conditions that deregulate the replication timing and the DNA replication fork progression lead to DNA replication stress. In response to escalating DNA replication stress conditions, DNA replication forks stall, regress and eventually collapse. Cells have evolved multiple recombination-dependent repair pathways for replication fork restart like the template switching, the recombination-dependent replication (RDR) and the break-induced replication (BIR). Although these pathways will retain cell's viability, they will do so at the expense of genomic instability. In our studies, we aimed to identify proteins that are important for replication fork restart under oncogene-induced DNA replication stress conditions. By carrying out flow-cytometry based siRNA screenings we identified 6 proteins (POLD3, POLD4, RAD52, MUS81, SMARCAL1 and ZRANB3) that are required for S-phase progression in DNA replication stress conditions.[..]

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Citation (ISO format)
SOTIRIOU, Sotirios. Mechanisms underlying genomic instability in human cancers. Doctoral Thesis, 2016. doi: 10.13097/archive-ouverte/unige:81482
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Creation16/02/2016 12:14:00
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Update15/03/2023 00:11:50
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