The role of NUCKS in DNA repair

<p>NUCKS is a vertebrate-specific, extensively post-translationally modified transcriptional regulator whose over- and under- expression is associated with cancer and obesity, respectively. We have previously found that NUCKS protein levels increase in DNA-damaged cells, and other studies have...

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Main Author: Hume, S
Other Authors: Dianov, G
Format: Thesis
Published: 2016
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author Hume, S
author2 Dianov, G
author_facet Dianov, G
Hume, S
author_sort Hume, S
collection OXFORD
description <p>NUCKS is a vertebrate-specific, extensively post-translationally modified transcriptional regulator whose over- and under- expression is associated with cancer and obesity, respectively. We have previously found that NUCKS protein levels increase in DNA-damaged cells, and other studies have reported DNA damage-dependent NUCKS phosphorylation. However, the full impacts of NUCKS depletion on DNA damage repair has not been established. Addressing this question, we show that NUCKS depletion activates some DNA damage response proteins and might be associated with accumulation of DNA damage in cancer cells. Furthermore, the transcriptional targets for NUCKS are poorly defined. To this end, we couple data from a published ChIP-Seq analysis for NUCKS with a bioinformatics approach to identify genes coexpressed with NUCKS in cancer patient samples and cell lines. We identify a number of genes, including many involved in DNA repair. We correspondingly find that NUCKS-depleted cells express lower levels of these genes and exhibit some hallmarks of their deficiency. Finally, we investigate how NUCKS’ putative transcriptional targets relate to disease, and therefore how NUCKS might be used as a biomarker for disease. </p>
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spelling oxford-uuid:2cb5578b-1824-4a69-a99e-126133c228342024-12-07T10:28:58ZThe role of NUCKS in DNA repairThesishttp://purl.org/coar/resource_type/c_bdccuuid:2cb5578b-1824-4a69-a99e-126133c22834ORA Deposit2016Hume, SDianov, GLegrand, A<p>NUCKS is a vertebrate-specific, extensively post-translationally modified transcriptional regulator whose over- and under- expression is associated with cancer and obesity, respectively. We have previously found that NUCKS protein levels increase in DNA-damaged cells, and other studies have reported DNA damage-dependent NUCKS phosphorylation. However, the full impacts of NUCKS depletion on DNA damage repair has not been established. Addressing this question, we show that NUCKS depletion activates some DNA damage response proteins and might be associated with accumulation of DNA damage in cancer cells. Furthermore, the transcriptional targets for NUCKS are poorly defined. To this end, we couple data from a published ChIP-Seq analysis for NUCKS with a bioinformatics approach to identify genes coexpressed with NUCKS in cancer patient samples and cell lines. We identify a number of genes, including many involved in DNA repair. We correspondingly find that NUCKS-depleted cells express lower levels of these genes and exhibit some hallmarks of their deficiency. Finally, we investigate how NUCKS’ putative transcriptional targets relate to disease, and therefore how NUCKS might be used as a biomarker for disease. </p>
spellingShingle Hume, S
The role of NUCKS in DNA repair
title The role of NUCKS in DNA repair
title_full The role of NUCKS in DNA repair
title_fullStr The role of NUCKS in DNA repair
title_full_unstemmed The role of NUCKS in DNA repair
title_short The role of NUCKS in DNA repair
title_sort role of nucks in dna repair
work_keys_str_mv AT humes theroleofnucksindnarepair
AT humes roleofnucksindnarepair