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Life Sciences

St. John's University

Theses and Dissertations

Theses/Dissertations

Replication stress

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Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar Jan 2023

Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar

Theses and Dissertations

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Major part of DDR is coordinated by DNA damage checkpoint (DDC). In addition to DDC, eukaryotic cells also have DNA replication checkpoint (DRC) that is distinct from the DDC and specifically signals slowly progressing or arrested replication forks. DDR involves stalling or arrest of the cell cycle, initiation of DNA repair, and altered regulation of transcription, translation, and the ubiquitin-proteasome system. DDR also triggers transcription shut-off of histone genes. One of the key outcomes of DDC/DRC activation is the increased synthesis of the deoxyribonucleoside triphosphates (dNTPs), …


Mechanism Of Dna Damage Checkpoint (Ddc)- Mediated Repression Of Histone Mrnas And Role Of Acetyl-Coa In Histone Transcription, Madhura Bhagwat Jan 2021

Mechanism Of Dna Damage Checkpoint (Ddc)- Mediated Repression Of Histone Mrnas And Role Of Acetyl-Coa In Histone Transcription, Madhura Bhagwat

Theses and Dissertations

My dissertation contains two projects. The first project is focused on the mechanism of DNA damage checkpoint (DDC)- mediated repression of histone mRNAs. The second project deals with the role of acetyl-CoA in histone transcription. Proliferating cells coordinate histone and DNA synthesis to maintain correct stoichiometric amounts for chromatin assembly. Histone mRNA levels must be repressed when DNA replication is inhibited to prevent toxicity and genome instability due to free non-chromatinized histone proteins. In the first project we show that, unlike in mammalian cells, DNA replication stress does not trigger decay of histone mRNAs in the yeast Saccharomyces cerevisiae. However, …