DNA replication timing and higher-order nuclear organization determine single nucleotide substitution patterns in cancer genomes

DSpace/Manakin Repository

DNA replication timing and higher-order nuclear organization determine single nucleotide substitution patterns in cancer genomes

Citable link to this page

 

 
Title: DNA replication timing and higher-order nuclear organization determine single nucleotide substitution patterns in cancer genomes
Author: Liu, Lin; De, Subhajyoti; Michor, Franziska

Note: Order does not necessarily reflect citation order of authors.

Citation: Liu, Lin, Subhajyoti De, and Franziska Michor. 2013. “DNA replication timing and higher-order nuclear organization determine single nucleotide substitution patterns in cancer genomes.” Nature communications 4 (1): 1502. doi:10.1038/ncomms2502. http://dx.doi.org/10.1038/ncomms2502.
Full Text & Related Files:
Abstract: Single nucleotide substitutions (SNS) are a defining characteristic of cancer genomes. Many SNS in cancer genomes arise due to errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes. Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic SNS is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features. Furthermore, some substitution signatures are more frequent in certain DNA replication timing zones. Finally, integrating data on higher-order nuclear organization, we found that genomic regions in close spatial proximity to late replicating domains display similar mutation spectra as the late replicating regions themselves. These data suggest that DNA replication timing together with higher-order genomic organization contribute to the patterns of SNS in normal and cancer genomes.
Published Version: doi:10.1038/ncomms2502
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633418/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717502
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters