Large XPF-dependent deletions following misrepair of a DNA double strand break are prevented by the RNA:DNA helicase Senataxin.
Large XPF-dependent deletions following misrepair of a DNA double strand break are prevented by the RNA:DNA helicase Senataxin.
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DOI：
10.1038/s41598-018-21806-y
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发表时间：
2018-03-01
影响因子：
4.6
通讯作者：
Sweet SMM
中科院分区：
文献类型：
--
作者：
Brustel J;Kozik Z;Gromak N;Savic V;Sweet SMM
Deletions and chromosome re-arrangements are common features of cancer cells. We have established a new two-component system reporting on epigenetic silencing or deletion of an actively transcribed gene adjacent to a double-strand break (DSB). Unexpectedly, we find that a targeted DSB results in a minority (<10%) misrepair event of kilobase deletions encompassing the DSB site and transcribed gene. Deletions are reduced upon RNaseH1 over-expression and increased after knockdown of the DNA:RNA helicase Senataxin, implicating a role for DNA:RNA hybrids. We further demonstrate that the majority of these large deletions are dependent on the 3′ flap endonuclease XPF. DNA:RNA hybrids were detected by DNA:RNA immunoprecipitation in our system after DSB generation. These hybrids were reduced by RNaseH1 over-expression and increased by Senataxin knock-down, consistent with a role in deletions. Overall, these data are consistent with DNA:RNA hybrid generation at the site of a DSB, mis-processing of which results in genome instability in the form of large deletions.
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影响因子：
14.9
作者：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
通讯作者：
Cerritelli SM
影响因子：
16
作者：
Hatchi, Elodie;Skourti-Stathaki, Konstantina;Ventz, Steffen;Pinello, Luca;Yen, Angela;Kamieniarz-Gdula, Kinga;Dimitrov, Stoil;Pathania, Shailja;McKinney, Kristine M.;Eaton, Matthew L.;Kellis, Manolis;Hill, Sarah J.;Parmigiani, Giovanni;Proudfoot, Nicholas J.;Livingston, David M.
通讯作者：
Livingston, David M.
影响因子：
14.9
作者：
Al-Minawi AZ;Saleh-Gohari N;Helleday T
通讯作者：
Helleday T
DOI：
10.1073/pnas.95.9.5172
发表时间：
1998-04-28
影响因子：
11.1
作者：
Liang, F;Han, MG;Jasin, M
通讯作者：
Jasin, M
影响因子：
4.5
作者：
García-Rubio ML;Pérez-Calero C;Barroso SI;Tumini E;Herrera-Moyano E;Rosado IV;Aguilera A
通讯作者：
Aguilera A