UNIGE document Doctoral Thesis
previous document  unige:94383  next document
add to browser collection
Title

Mechanisms of oncogene-induced DNA replication stress

Author
Director
Defense Thèse de doctorat : Univ. Genève, 2017 - Sc. 5070 - 2017/04/28
Abstract Oncogenes in human cancers induce DNA replication stress and genomic instability. Towards elucidating the underlying molecular mechanisms, we monitored origin firing in human cells after inducibly activating the proto-oncogenes cyclin E or MYC. Both oncogenes led to firing of novel replication origins within highly transcribed genes. These novel origins were normally suppressed by transcription during G1, but precocious entry into S phase allowed origin firing within genomic regions that had not yet been transcribed. Forks from oncogene-induced origins were prone to collapse, due to conflicts between replication and transcription, and were associated with DNA double-strand break formation and chromosomal rearrangement breakpoints. We propose that in normal cells, initiation of DNA replication is mostly restricted to non-transcribed genomic regions, whereas shortening of G1 in cancer cells leads to origin firing within transcribed genes, fork collapse and genomic instability.
Identifiers
URN: urn:nbn:ch:unige-943839
Full text
Thesis (16.3 MB) - private document Private access (until 2018-05-19)
Structures
Research group Groupe Halazonetis
Citation
(ISO format)
MACHERET, Morgane. Mechanisms of oncogene-induced DNA replication stress. Université de Genève. Thèse, 2017. https://archive-ouverte.unige.ch/unige:94383

77 hits

1 download

Update

Deposited on : 2017-05-22

Export document
Format :
Citation style :