Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling
Autoři
CHAKI, Moumita; Rannar AIRIK; Amiya K. GHOSH; Rachel H. GILES; Rui CHEN; Gisela G. SLAATS; Hui WANG; Toby W. HURD; Weibin ZHOU; Andrew CLUCKEY; Heon-Yung GEE; Gokul RAMASWAMI; Chen-Jei HONG; Bruce A. HAMILTON,; Igor ČERVENKA; Sri Ranjani GANJI; Vítězslav BRYJA; Heleen H. ARTS; Jeroen VAN REEUWIJK; Machteld M. OUD; Stef J.F. LETTEBOER; Ronald ROEPMAN; Hervé HUSSON; Oxana IBRAGHIMOV-BESKROVNAYA; Takayuky YSUNAGA; Gerd WALZ; Lorraine ELEY; Bernhard SCHERMER; John A. SYAER; Max C. LIEBAU; Thomas BENZING; Stephanie LE CORRE; Iain DRUMMOND; Sabine JANSSEN; Susan J. ALLEN; Sivakumar NATARAJAN; John F. O TOOLE; Massimo ATTANASIO; Sophie SAUNIER; Corinne ANTIGNAC; Robert K. KOENEKOOP; Huanan REN; Irma LOPEZ; Ahmet NAYIR; Corinne STOETZEL; Helene DOLLFUS; Rustin MASSOUDI; Joseph G. GLEESON; Sharon P. ANDREOLI; Dan G. DOHERTY; Anna LINDSTRAD; Christelle GOLZIO; Nicholas KATSANIS; Lars PAPE; Emad B. ABBOUD; Ali A. AL-RAJHI; Richard A. LEWIS; Heymut OMRAN; Eva LEE; Shaohui WANG; JoAnn M. SEKIGUCHI; Rudel SAUNDERS; Colin A. JOHNSON; Elizabeth GARNER; Katja VANSELOW; Jens S. ANDERSEN; Joseph SHLOMAI; Gudrun NURNBERG; Peter NURNBERG; Shawn LEVY; Agata SMOGORZEWSKA; Edgar A. OTTO a Friedhelm HILDEBRANDT
Vydání
Cell, United States of America, Cell Press, Cambridge, MA, USA, 2012, 0092-8674
Nephronophthisis-related ciliopathies (NPHP-RC) are degenerative recessive diseases that affect kidney, retina, and brain. Genetic defects in NPHP gene products that localize to cilia and centrosomes defined them as "ciliopathies." However, disease mechanisms remain poorly understood. Here, we identify by whole-exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing NPHP-RC. All three genes function within the DNA damage response (DDR) pathway. We demonstrate that, upon induced DNA damage, the NPHP-RC proteins ZNF423, CEP164, and NPHP10 colocalize to nuclear foci positive for TIP60, known to activate ATM at sites of DNA damage. We show that knockdown of CEP164 or ZNF423 causes sensitivity to DNA damaging agents and that cep164 knockdown in zebrafish results in dysregulated DDR and an NPHP-RC phenotype. Our findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR.
Návaznosti
MSM0021622430, záměr
Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie
1658, interní kód MU
Název: EMBO Young Investigator Programme (Akronym: EMBO)
Investor: EMBO (European Molecular Biology Organization), EMBO Young Investigator Programme
CHAKI, Moumita; Rannar AIRIK; Amiya K. GHOSH; Rachel H. GILES; Rui CHEN; Gisela G. SLAATS; Hui WANG; Toby W. HURD; Weibin ZHOU; Andrew CLUCKEY; Heon-Yung GEE; Gokul RAMASWAMI; Chen-Jei HONG; Bruce A. HAMILTON,; Igor ČERVENKA; Sri Ranjani GANJI; Vítězslav BRYJA; Heleen H. ARTS; Jeroen VAN REEUWIJK; Machteld M. OUD; Stef J.F. LETTEBOER; Ronald ROEPMAN; Hervé HUSSON; Oxana IBRAGHIMOV-BESKROVNAYA; Takayuky YSUNAGA; Gerd WALZ; Lorraine ELEY; Bernhard SCHERMER; John A. SYAER; Max C. LIEBAU; Thomas BENZING; Stephanie LE CORRE; Iain DRUMMOND; Sabine JANSSEN; Susan J. ALLEN; Sivakumar NATARAJAN; John F. O TOOLE; Massimo ATTANASIO; Sophie SAUNIER; Corinne ANTIGNAC; Robert K. KOENEKOOP; Huanan REN; Irma LOPEZ; Ahmet NAYIR; Corinne STOETZEL; Helene DOLLFUS; Rustin MASSOUDI; Joseph G. GLEESON; Sharon P. ANDREOLI; Dan G. DOHERTY; Anna LINDSTRAD; Christelle GOLZIO; Nicholas KATSANIS; Lars PAPE; Emad B. ABBOUD; Ali A. AL-RAJHI; Richard A. LEWIS; Heymut OMRAN; Eva LEE; Shaohui WANG; JoAnn M. SEKIGUCHI; Rudel SAUNDERS; Colin A. JOHNSON; Elizabeth GARNER; Katja VANSELOW; Jens S. ANDERSEN; Joseph SHLOMAI; Gudrun NURNBERG; Peter NURNBERG; Shawn LEVY; Agata SMOGORZEWSKA; Edgar A. OTTO a Friedhelm HILDEBRANDT. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell. United States of America: Cell Press, Cambridge, MA, USA, 2012, roč. 150, č. 3, s. 533-548. ISSN 0092-8674. Dostupné z: https://doi.org/10.1016/j.cell.2012.06.028.
@article{1094509, author = {Chaki, Moumita and Airik, Rannar and Ghosh, Amiya K. and Giles, Rachel H. and Chen, Rui and Slaats, Gisela G. and Wang, Hui and Hurd, Toby W. and Zhou, Weibin and Cluckey, Andrew and Gee, HeonandYung and Ramaswami, Gokul and Hong, ChenandJei and Hamilton,, Bruce A. and Červenka, Igor and Ganji, Sri Ranjani and Bryja, Vítězslav and Arts, Heleen H. and van Reeuwijk, Jeroen and Oud, Machteld M. and Letteboer, Stef J.F. and Roepman, Ronald and Husson, Hervé and IbraghimovandBeskrovnaya, Oxana and Ysunaga, Takayuky and Walz, Gerd and Eley, Lorraine and Schermer, Bernhard and Syaer, John A. and Liebau, Max C. and Benzing, Thomas and Le Corre, Stephanie and Drummond, Iain and Janssen, Sabine and Allen, Susan J. and Natarajan, Sivakumar and O Toole, John F. and Attanasio, Massimo and Saunier, Sophie and Antignac, Corinne and Koenekoop, Robert K. and Ren, Huanan and Lopez, Irma and Nayir, Ahmet and Stoetzel, Corinne and Dollfus, Helene and Massoudi, Rustin and Gleeson, Joseph G. and Andreoli, Sharon P. and Doherty, Dan G. and Lindstrad, Anna and Golzio, Christelle and Katsanis, Nicholas and Pape, Lars and Abboud, Emad B. and AlandRajhi, Ali A. and Lewis, Richard A. and Omran, Heymut and Lee, Eva and Wang, Shaohui and Sekiguchi, JoAnn M. and Saunders, Rudel and Johnson, Colin A. and Garner, Elizabeth and Vanselow, Katja and Andersen, Jens S. and Shlomai, Joseph and Nurnberg, Gudrun and Nurnberg, Peter and Levy, Shawn and Smogorzewska, Agata and Otto, Edgar A. and Hildebrandt, Friedhelm}, article_location = {United States of America}, article_number = {3}, doi = {https://doi.org/10.1016/j.cell.2012.06.028}, keywords = {NPHP; CEP 164; ZNF423; renal ciliopathies}, language = {eng}, issn = {0092-8674}, journal = {Cell}, title = {Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling}, volume = {150}, year = {2012} }
TY - JOUR ID - 1094509 AU - Chaki, Moumita - Airik, Rannar - Ghosh, Amiya K. - Giles, Rachel H. - Chen, Rui - Slaats, Gisela G. - Wang, Hui - Hurd, Toby W. - Zhou, Weibin - Cluckey, Andrew - Gee, Heon-Yung - Ramaswami, Gokul - Hong, Chen-Jei - Hamilton,, Bruce A. - Červenka, Igor - Ganji, Sri Ranjani - Bryja, Vítězslav - Arts, Heleen H. - van Reeuwijk, Jeroen - Oud, Machteld M. - Letteboer, Stef J.F. - Roepman, Ronald - Husson, Hervé - Ibraghimov-Beskrovnaya, Oxana - Ysunaga, Takayuky - Walz, Gerd - Eley, Lorraine - Schermer, Bernhard - Syaer, John A. - Liebau, Max C. - Benzing, Thomas - Le Corre, Stephanie - Drummond, Iain - Janssen, Sabine - Allen, Susan J. - Natarajan, Sivakumar - O Toole, John F. - Attanasio, Massimo - Saunier, Sophie - Antignac, Corinne - Koenekoop, Robert K. - Ren, Huanan - Lopez, Irma - Nayir, Ahmet - Stoetzel, Corinne - Dollfus, Helene - Massoudi, Rustin - Gleeson, Joseph G. - Andreoli, Sharon P. - Doherty, Dan G. - Lindstrad, Anna - Golzio, Christelle - Katsanis, Nicholas - Pape, Lars - Abboud, Emad B. - Al-Rajhi, Ali A. - Lewis, Richard A. - Omran, Heymut - Lee, Eva - Wang, Shaohui - Sekiguchi, JoAnn M. - Saunders, Rudel - Johnson, Colin A. - Garner, Elizabeth - Vanselow, Katja - Andersen, Jens S. - Shlomai, Joseph - Nurnberg, Gudrun - Nurnberg, Peter - Levy, Shawn - Smogorzewska, Agata - Otto, Edgar A. - Hildebrandt, Friedhelm PY - 2012 TI - Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling JF - Cell VL - 150 IS - 3 SP - 533-548 EP - 533-548 PB - Cell Press, Cambridge, MA, USA SN - 00928674 KW - NPHP KW - CEP 164 KW - ZNF423 KW - renal ciliopathies N2 - Nephronophthisis-related ciliopathies (NPHP-RC) are degenerative recessive diseases that affect kidney, retina, and brain. Genetic defects in NPHP gene products that localize to cilia and centrosomes defined them as "ciliopathies." However, disease mechanisms remain poorly understood. Here, we identify by whole-exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing NPHP-RC. All three genes function within the DNA damage response (DDR) pathway. We demonstrate that, upon induced DNA damage, the NPHP-RC proteins ZNF423, CEP164, and NPHP10 colocalize to nuclear foci positive for TIP60, known to activate ATM at sites of DNA damage. We show that knockdown of CEP164 or ZNF423 causes sensitivity to DNA damaging agents and that cep164 knockdown in zebrafish results in dysregulated DDR and an NPHP-RC phenotype. Our findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR. ER -
CHAKI, Moumita; Rannar AIRIK; Amiya K. GHOSH; Rachel H. GILES; Rui CHEN; Gisela G. SLAATS; Hui WANG; Toby W. HURD; Weibin ZHOU; Andrew CLUCKEY; Heon-Yung GEE; Gokul RAMASWAMI; Chen-Jei HONG; Bruce A. HAMILTON,; Igor ČERVENKA; Sri Ranjani GANJI; Vítězslav BRYJA; Heleen H. ARTS; Jeroen VAN REEUWIJK; Machteld M. OUD; Stef J.F. LETTEBOER; Ronald ROEPMAN; Hervé HUSSON; Oxana IBRAGHIMOV-BESKROVNAYA; Takayuky YSUNAGA; Gerd WALZ; Lorraine ELEY; Bernhard SCHERMER; John A. SYAER; Max C. LIEBAU; Thomas BENZING; Stephanie LE CORRE; Iain DRUMMOND; Sabine JANSSEN; Susan J. ALLEN; Sivakumar NATARAJAN; John F. O TOOLE; Massimo ATTANASIO; Sophie SAUNIER; Corinne ANTIGNAC; Robert K. KOENEKOOP; Huanan REN; Irma LOPEZ; Ahmet NAYIR; Corinne STOETZEL; Helene DOLLFUS; Rustin MASSOUDI; Joseph G. GLEESON; Sharon P. ANDREOLI; Dan G. DOHERTY; Anna LINDSTRAD; Christelle GOLZIO; Nicholas KATSANIS; Lars PAPE; Emad B. ABBOUD; Ali A. AL-RAJHI; Richard A. LEWIS; Heymut OMRAN; Eva LEE; Shaohui WANG; JoAnn M. SEKIGUCHI; Rudel SAUNDERS; Colin A. JOHNSON; Elizabeth GARNER; Katja VANSELOW; Jens S. ANDERSEN; Joseph SHLOMAI; Gudrun NURNBERG; Peter NURNBERG; Shawn LEVY; Agata SMOGORZEWSKA; Edgar A. OTTO a Friedhelm HILDEBRANDT. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. \textit{Cell}. United States of America: Cell Press, Cambridge, MA, USA, 2012, roč.~150, č.~3, s.~533-548. ISSN~0092-8674. Dostupné z: https://doi.org/10.1016/j.cell.2012.06.028.