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MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks.
Singh, Dharmendra Kumar; Pandita, Raj K; Singh, Mayank; Chakraborty, Sharmistha; Hambarde, Shashank; Ramnarain, Deepti; Charaka, Vijaya; Ahmed, Kazi Mokim; Hunt, Clayton R; Pandita, Tej K.
Afiliação
  • Singh DK; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA dksingh2006@gmail.com tpandita@houstonmethodist.org.
  • Pandita RK; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA.
  • Singh M; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  • Chakraborty S; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA.
  • Hambarde S; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA.
  • Ramnarain D; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  • Charaka V; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA.
  • Ahmed KM; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA.
  • Hunt CR; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA.
  • Pandita TK; Department of Radiation Oncology, Weill Cornell Medical College, The Houston Methodist Research Institute, Houston, Texas, USA dksingh2006@gmail.com tpandita@houstonmethodist.org.
Mol Cell Biol ; 38(6)2018 03 15.
Article em En | MEDLINE | ID: mdl-29298824
The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation; however, its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted of MOF and under replicative stress induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, a higher frequency of S-phase-specific chromosome damage, and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing. MOF interacted with PCNA, a key coordinator of replication and repair machinery at replication forks, and affected its ubiquitination and recruitment to the DNA damage site. Depletion of MOF, therefore, compromised the DNA damage repair response as evidenced by decreased Mre11, RPA70, Rad51, and PCNA focus formation, reduced DNA end resection, and decreased CHK1 phosphorylation in cells after exposure to hydroxyurea or cisplatin. These results support the argument that MOF plays an important role in suppressing replication stress induced by genotoxic agents at several stages during the DNA damage response.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Camptotecina / Cisplatino / Replicação do DNA / Histona Acetiltransferases / Hidroxiureia / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Camptotecina / Cisplatino / Replicação do DNA / Histona Acetiltransferases / Hidroxiureia / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article