Imperial College London
Dr Samuel Marguerat

DrSamuelMarguerat

Faculty of Natural Sciences, Department of Mathematics

Visiting Researcher
 
 
 
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Contact

 

+44 (0)20 3313 8331samuel.marguerat Website

 
 
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Location

 

5003CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Blaikley:2014:nar/gku190,
author = {Blaikley, EJ and Tinline-Purvis, H and Kasparek, TR and Marguerat, S and Sarkar, S and Hulme, L and Hussey, S and Wee, BY and Deegan, RS and Walker, CA and Pai, CC and Bähler, J and Nakagawa, T and Humphrey, TC},
doi = {nar/gku190},
journal = {Nucleic Acids Research},
pages = {5644--5656},
title = {The DNA damage checkpoint pathway promotes extensive resection and nucleotide synthesis to facilitate homologous recombination repair and genome stability in fission yeast.},
url = {http://dx.doi.org/10.1093/nar/gku190},
volume = {42},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - DNA double-strand breaks (DSBs) can cause chromosomal rearrangements and extensive loss of heterozygosity (LOH), hallmarks of cancer cells. Yet, how such events are normally suppressed is unclear. Here we identify roles for the DNA damage checkpoint pathway in facilitating homologous recombination (HR) repair and suppressing extensive LOH and chromosomal rearrangements in response to a DSB. Accordingly, deletion of Rad3(ATR), Rad26ATRIP, Crb2(53BP1) or Cdc25 overexpression leads to reduced HR and increased break-induced chromosome loss and rearrangements. We find the DNA damage checkpoint pathway facilitates HR, in part, by promoting break-induced Cdt2-dependent nucleotide synthesis. We also identify additional roles for Rad17, the 9-1-1 complex and Chk1 activation in facilitating break-induced extensive resection and chromosome loss, thereby suppressing extensive LOH. Loss of Rad17 or the 9-1-1 complex results in a striking increase in break-induced isochromosome formation and very low levels of chromosome loss, suggesting the 9-1-1 complex acts as a nuclease processivity factor to facilitate extensive resection. Further, our data suggest redundant roles for Rad3ATR and Exo1 in facilitating extensive resection. We propose that the DNA damage checkpoint pathway coordinates resection and nucleotide synthesis, thereby promoting efficient HR repair and genome stability.
AU  - Blaikley,EJ
AU  - Tinline-Purvis,H
AU  - Kasparek,TR
AU  - Marguerat,S
AU  - Sarkar,S
AU  - Hulme,L
AU  - Hussey,S
AU  - Wee,BY
AU  - Deegan,RS
AU  - Walker,CA
AU  - Pai,CC
AU  - Bähler,J
AU  - Nakagawa,T
AU  - Humphrey,TC
DO  - nar/gku190
EP  - 5656
PY  - 2014///
SN  - 1362-4962
SP  - 5644
TI  - The DNA damage checkpoint pathway promotes extensive resection and nucleotide synthesis to facilitate homologous recombination repair and genome stability in fission yeast.
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gku190
UR  - http://hdl.handle.net/10044/1/21980
VL  - 42
ER  -
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