s41467-018-03098-y.pdf (6.38 MB)
53BP1 can limit sister-chromatid rupture and rearrangements driven by a distinct ultrafine DNA bridging-breakage process
journal contribution
posted on 2023-06-09, 12:06 authored by Ankana Tiwari, Owen Addis, Kok-Lung ChanKok-Lung ChanChromosome missegregation acts as one of the driving forces for chromosome instability and cancer development. Here, we find that in human cancer cells, HeLa and U2OS, depletion of 53BP1 (p53-binding protein 1) exacerbates chromosome non-disjunction resulting from a new type of sister-chromatid intertwinement, which is distinct from FANCD2-associated ultrafine DNA bridges (UFBs) induced by replication stress. Importantly, the sister DNA intertwinements trigger gross chromosomal rearrangements through a distinct process, named sister-chromatid rupture and bridging. In contrast to conventional anaphase bridge-breakage models, we demonstrate that chromatid axes of the intertwined sister-chromatids rupture prior to the breakage of the DNA bridges. Consequently, the ruptured sister arms remain tethered and cause signature chromosome rearrangements, including whole-arm (Robertsonian-like) translocation/deletion and isochromosome formation. Therefore, our study reveals a hitherto unreported chromatid damage phenomenon mediated by sister DNA intertwinements that may help to explain the development of complex karyotypes in tumour cells.
Funding
Molecular basis of inheritable DNA lesions on genome transformation; G1408; WELLCOME TRUST; 104178/Z/14/Z
History
Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature Publishing GroupExternal DOI
Issue
1Volume
9Page range
1-17Article number
a677Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Advanced Communications, Mobile Technology and IoT (ACMI) Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-02-14First Open Access (FOA) Date
2018-02-14First Compliant Deposit (FCD) Date
2018-02-14Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC