| dc.contributor |
MRC - Medical Research Council |
|
| dc.contributor |
Taylor, Martin |
|
| dc.creator |
Taylor, Martin |
|
| dc.creator |
Kemp, Harriet |
|
| dc.creator |
Marion de Procé, Sophie |
|
| dc.creator |
Reijns, Martin |
|
| dc.creator |
Ding, James |
|
| dc.creator |
Jackson, Andrew |
|
| dc.date |
2015-01-23T13:45:33Z |
|
| dc.date |
2015-01-26T13:45:33Z |
|
| dc.date.accessioned |
2023-02-17T20:52:07Z |
|
| dc.date.available |
2023-02-17T20:52:07Z |
|
| dc.identifier |
Taylor, Martin; Kemp, Harriet; Marion de Procé, Sophie; Reijns, Martin; Ding, James; Jackson, Andrew. (2015). Lagging strand replication shapes the mutational landscape of the genome, [dataset]. University of Edinburgh. MRC Institute of Genetics and Molecular Medicine. MRC Human Genetics Unit. https://doi.org/10.7488/ds/204. |
|
| dc.identifier |
https://hdl.handle.net/10283/701 |
|
| dc.identifier |
https://doi.org/10.7488/ds/204 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/243964 |
|
| dc.description |
The origin of mutations is central to understanding evolution and of key relevance to health. Variation occurs non-randomly across the genome, and mechanisms for this remain to be defined. Here we report that the 5' ends of Okazaki fragments have significantly increased levels of nucleotide substitution, indicating a replicative origin for such mutations. Using a novel method, emRiboSeq, we map the genome-wide contribution of polymerases, and show that despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-alpha (Pol-alpha) is retained in vivo, comprising ~1.5% of the mature genome. We propose that DNA-binding proteins that rapidly re-associate post-replication act as partial barriers to Pol-delta-mediated displacement of Pol-alpha-synthesized DNA, resulting in incorporation of such Pol-alpha tracts and increased mutation rates at specific sites. We observe a mutational cost to chromatin and regulatory protein binding, resulting in mutation hotspots at regulatory elements, with signatures of this process detectable in both yeast and humans. |
|
| dc.description |
See dataShareREADME.txt |
|
| dc.format |
application/octet-stream |
|
| dc.format |
text/plain |
|
| dc.language |
eng |
|
| dc.publisher |
University of Edinburgh. MRC Institute of Genetics and Molecular Medicine. MRC Human Genetics Unit |
|
| dc.relation |
https://doi.org/10.1038/nature14183 |
|
| dc.relation |
https://github.com/taylorLab/LaggingStrand |
|
| dc.relation |
Reijns, MAM, Kemp, H, Ding, J, Marion de Procé, S, Jackson, P, Taylor, M. (2015) "Lagging-strand replication shapes the mutational landscape of the genome" Nature, https://doi.org/10.1038/nature14183 . |
|
| dc.source |
http://www.sciencemag.org/site/feature/data/raghu1064351/SmoothedPooledHLData/smoothedpooledHLdata.html |
|
| dc.source |
http://hgdownload.soe.ucsc.edu/goldenPath/sacCer3/multiz7way/maf/ |
|
| dc.source |
ftp://ftp.sanger.ac.uk/pub/users/dmc/yeast/latest/misc.tgz |
|
| dc.subject |
DNA |
|
| dc.subject |
mutation |
|
| dc.subject |
replication |
|
| dc.subject |
lagging strand |
|
| dc.subject |
Biological Sciences::Molecular Biology Biophysics and Biochemistry |
|
| dc.title |
Lagging strand replication shapes the mutational landscape of the genome |
|
| dc.type |
dataset |
|