Delayed replication timing leads to delayed mitotic chromosome condensation and chromosomal instability of chromosome translocations
TLDR
It is suggested that certain chromosomal rearrangements found in tumor cells cause a significant delay in replication timing of the entire chromosome that subsequently results in delayed mitotic chromosome condensation and ultimately in chromosomal instability.Abstract:
Chromosomal rearrangements are found in virtually all types of human cancers. We show that certain chromosome translocations display a delay in mitotic chromosome condensation that is associated with a delay in the mitosis-specific phosphorylation of histone H3. This delay in mitotic condensation is preceded by a delay in both the initiation as well as the completion of chromosome replication. In addition, chromosomes with this phenotype participate in numerous secondary translocations and rearrangements. Chromosomes with this phenotype were detected in five of seven tumor-derived cell lines and in five of thirteen primary tumor samples. These data suggest that certain chromosomal rearrangements found in tumor cells cause a significant delay in replication timing of the entire chromosome that subsequently results in delayed mitotic chromosome condensation and ultimately in chromosomal instability.read more
Citations
More filters
Journal ArticleDOI
DNA breaks and chromosome pulverization from errors in mitosis
Karen Crasta,Neil J. Ganem,Neil J. Ganem,Regina Dagher,Regina Dagher,Alexandra B. Lantermann,Elena Ivanova,Yunfeng Pan,Luigi Nezi,Alexei Protopopov,Dipanjan Chowdhury,David Pellman,David Pellman +12 more
TL;DR: A mechanism by which errors in mitotic chromosome segregation generate DNA breaks via the formation of structures called micronuclei is identified, which potentially lead to mutations and chromosome rearrangements that can integrate into the genome.
Journal ArticleDOI
Replication timing and transcriptional control: beyond cause and effect-part III.
TL;DR: Mounting evidence supports a model in which replication timing is both cause and consequence of chromatin structure by providing a means to inherit chromatin states that, in turn, regulate replication timing in the subsequent cell cycle.
Journal ArticleDOI
Replication timing and transcriptional control: beyond cause and effect
TL;DR: Mounting evidence supports a model in which replication timing is both cause and consequence of chromatin structure by providing a means to inherit chromatin states that, in turn, regulate replication timing in the subsequent cell cycle.
Journal ArticleDOI
Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements
TL;DR: The impact of massive chromosomal change for the development of diseases such as cancer and for evolution more generally is considered and current models for underlying mechanisms are summarized.
Journal ArticleDOI
Control of DNA replication timing in the 3D genome.
TL;DR: The recent identification of specific DNA sequences and long non-coding RNAs that regulate DNA replication timing is providing key insights into the roles of replication timing and into timing and 3D organization.
References
More filters
Journal ArticleDOI
Genetic instabilities in human cancers
TL;DR: There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
Journal ArticleDOI
Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation.
Michael J. Hendzel,Y Wei,Michael A. Mancini,A. Van Hooser,Tamara A. Ranalli,Bill R. Brinkley,David P. Bazett-Jones,C D Allis +7 more
TL;DR: It is proposed that the singular phosphorylation of the amino-terminus of histone H3 may be involved in facilitating two key functions during mitosis: (1) regulate protein-protein interactions to promote binding of trans-acting factors that “drive” chromatin condensation as cells enter M-phase and (2) coordinate chromatin decondensation associated with M- phase.
Book
Catalog of chromosome aberrations in cancer
TL;DR: This poster presents a probabilistic procedure to count the number of chromosomes in the nucleus using a simple “spatially aggregating” procedure called “spot-spot analysis”.
Journal ArticleDOI
Phosphorylation of Histone H3 Is Required for Proper Chromosome Condensation and Segregation
TL;DR: It is demonstrated that H3 serine 10 phosphorylation is causally linked to chromosome condensation and segregation in vivo and is required for proper chromosome dynamics.
Journal ArticleDOI
A breakpoint map of recurrent chromosomal rearrangements in human neoplasia.
TL;DR: A computer program is developed to ascertain, for the first time, all recurrent structural abnormalities in all haematological malignancies and solid tumours published up to June 19, which should help in directing future efforts aimed at identifying the molecular mechanisms involved in tumorigenesis.
Related Papers (5)
Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development
Philip J. Stephens,Christopher Greenman,Beiyuan Fu,Fengtang Yang,Graham R. Bignell,Laura Mudie,Erin Pleasance,King Wai Lau,David Beare,Lucy Stebbings,Stuart McLaren,Meng-Lay Lin,David J. McBride,Ignacio Varela,Serena Nik-Zainal,Catherine Leroy,Mingming Jia,Andrew Menzies,Adam Butler,Jon W. Teague,Michael A. Quail,John Burton,Harold Swerdlow,Nigel P. Carter,Laura Morsberger,Christine A. Iacobuzio-Donahue,George A. Follows,Anthony R. Green,Adrienne M. Flanagan,Adrienne M. Flanagan,Michael R. Stratton,P. Andrew Futreal,Peter J. Campbell,Peter J. Campbell +33 more