Next Article in Journal
A Dual Face of APE1 in the Maintenance of Genetic Stability in Monocytes: An Overview of the Current Status and Future Perspectives
Next Article in Special Issue
Protective Mechanisms Against DNA Replication Stress in the Nervous System
Previous Article in Journal
Nuclear Functions of TOR: Impact on Transcription and the Epigenome
Previous Article in Special Issue
Location, Location, Location: The Role of Nuclear Positioning in the Repair of Collapsed Forks and Protection of Genome Stability
Open AccessFeature PaperReview

DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons

1
CNRS UMR9019 Genome Integrity and Cancers, Université Paris Saclay, Gustave Roussy, 94805 Villejuif, France
2
UMR144 Cell Biology and Cancer, Institut Curie, 75005 Paris, France
*
Author to whom correspondence should be addressed.
Genes 2020, 11(6), 642; https://doi.org/10.3390/genes11060642
Received: 11 May 2020 / Revised: 4 June 2020 / Accepted: 8 June 2020 / Published: 10 June 2020
(This article belongs to the Special Issue Protective Mechanisms Against DNA Replication Stress)
Chromosomal instability (CIN) is associated with many human diseases, including neurodevelopmental or neurodegenerative conditions, age-related disorders and cancer, and is a key driver for disease initiation and progression. A major source of structural chromosome instability (s-CIN) leading to structural chromosome aberrations is “replication stress”, a condition in which stalled or slowly progressing replication forks interfere with timely and error-free completion of the S phase. On the other hand, mitotic errors that result in chromosome mis-segregation are the cause of numerical chromosome instability (n-CIN) and aneuploidy. In this review, we will discuss recent evidence showing that these two forms of chromosomal instability can be mechanistically interlinked. We first summarize how replication stress causes structural and numerical CIN, focusing on mechanisms such as mitotic rescue of replication stress (MRRS) and centriole disengagement, which prevent or contribute to specific types of structural chromosome aberrations and segregation errors. We describe the main outcomes of segregation errors and how micronucleation and aneuploidy can be the key stimuli promoting inflammation, senescence, or chromothripsis. At the end, we discuss how CIN can reduce cellular fitness and may behave as an anticancer barrier in noncancerous cells or precancerous lesions, whereas it fuels genomic instability in the context of cancer, and how our current knowledge may be exploited for developing cancer therapies. View Full-Text
Keywords: DNA replication stress; chromosomal instability; chromosome segregation; mitosis; cancer; aneuploidy DNA replication stress; chromosomal instability; chromosome segregation; mitosis; cancer; aneuploidy
Show Figures

Figure 1

MDPI and ACS Style

Wilhelm, T.; Said, M.; Naim, V. DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons. Genes 2020, 11, 642.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop