English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The presence of extra chromosomes leads to genomic instability

Passerini, V., Ozeri-Galai, E., de Pagter, M. S., Donnelly, N., Schmalbrock, S., Kloosterman, W. P., et al. (2016). The presence of extra chromosomes leads to genomic instability. NATURE COMMUNICATIONS, 7: 10754. doi:10.1038/ncomms10754.

Item is

Files

show Files
hide Files
:
ncomms10754.pdf (Any fulltext), 3MB
Name:
ncomms10754.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
open access article
License:
-

Locators

show

Creators

show
hide
 Creators:
Passerini, Verena1, Author              
Ozeri-Galai, Efrat2, Author
de Pagter, Mirjam S.2, Author
Donnelly, Neysan1, Author              
Schmalbrock, Sarah1, Author              
Kloosterman, Wigard P.2, Author
Kerem, Batsheva2, Author
Storchova, Zuzana1, Author              
Affiliations:
1Storchova, Zuzana / Maintenance of Genome Stability, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565171              
2external, ou_persistent22              

Content

show
hide
Free keywords: ONCOGENE-INDUCED SENESCENCE; ANEUPLOID HUMAN-CELLS; DNA-DAMAGE; REPLICATION STRESS; FRAGILE SITES; HUMAN-DISEASE; MCM PROTEINS; CANCER-CELLS; STEM-CELLS; YEAST
 Abstract: Aneuploidy is a hallmark of cancer and underlies genetic disorders characterized by severe developmental defects, yet the molecular mechanisms explaining its effects on cellular physiology remain elusive. Here we show, using a series of human cells with defined aneuploid karyotypes, that gain of a single chromosome increases genomic instability. Next-generation sequencing and SNP-array analysis reveal accumulation of chromosomal rearrangements in aneuploids, with break point junction patterns suggestive of replication defects. Trisomic and tetrasomic cells also show increased DNA damage and sensitivity to replication stress. Strikingly, we find that aneuploidy-induced genomic instability can be explained by the reduced expression of the replicative helicase MCM2-7. Accordingly, restoring near-wild-type levels of chromatin-bound MCM helicase partly rescues the genomic instability phenotypes. Thus, gain of chromosomes triggers replication stress, thereby promoting genomic instability and possibly contributing to tumorigenesis.

Details

show
hide
Language(s): eng - English
 Dates: 2016
 Publication Status: Published online
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000371037200016
DOI: 10.1038/ncomms10754
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: NATURE COMMUNICATIONS
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 7 Sequence Number: 10754 Start / End Page: - Identifier: ISSN: 2041-1723