dc.contributor.advisor | Guettler S | |
dc.contributor.author | Xie, Y | |
dc.contributor.editor | Guettler, S | |
dc.date.accessioned | 2022-08-31T14:22:53Z | |
dc.date.available | 2022-08-31T14:22:53Z | |
dc.date.issued | 2022-08-25 | |
dc.identifier.citation | 2022 | en_US |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5353 | |
dc.description.abstract | Linear chromosomes present two major challenges, known as the end-replication and end-protection problems. The human shelterin complex is a dynamic assembly of six components, consisting of TRF1, TRF2, RAP1, TIN2, TPP1, and POT1. These proteins decorate the telomeres, protecting the ends by suppressing DNA-damage responses and regulating telomere length maintenance. Impairment in either of these functions can lead to multiple diseases. For instance, mutations in components of shelterin and telomerase cause the severe, progressive genetic disorder dyskeratosis congenita (DC), where the signs and symptoms reflect multi-system stem cell failure. Moreover, mutations in multiple shelterin subunits have been implicated in a wide range of human malignancies.
Over the past three decades, the protein-protein and protein-DNA interactions within shelterin has been extensively characterised. High-resolution structures have been solved for domains and captured domain-peptide interactions. However, the overall architecture of human shelterin complexes is still unknown. Here, I report the expression and purification of the full shelterin complex and four subcomplexes. I describe biochemical and biophysical studies to explore the size and stoichiometry of shelterin complexes, and their affinity for telomeric and non-telomeric DNA substrates. Integrating data from crosslinking mass spectrometry and negative-stain electron microscopy, I illustrate that human shelterin subunits can assemble into dynamic complexes that are heterogeneous in both composition and conformation. | |
dc.language.iso | eng | en_US |
dc.publisher | Institute of Cancer Research (University Of London) | en_US |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | en_US |
dc.title | A biochemical analysis of human shelterin complexes | en_US |
dc.type | Thesis or Dissertation | |
dcterms.accessRights | Public | |
dc.date.updated | 2022-08-31T14:18:32Z | |
rioxxterms.version | AO | en_US |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | en_US |
rioxxterms.licenseref.startdate | 2022-08-25 | |
rioxxterms.type | Thesis | en_US |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/17/18 Starting Cohort | |
icr.researchteam | Struct Biol Cell Signal | en_US |
dc.contributor.icrauthor | Xie, Yexin | |
uketdterms.institution | Institute of Cancer Research | |
uketdterms.qualificationlevel | Doctoral | |
uketdterms.qualificationname | Ph.D | |
icr.provenance | Deposited by Mr Barry Jenkins (impersonating Ms Yexin Xie) on 2022-08-31. Deposit type is initial. No. of files: 1. Files: Y Xie PhD thesis.pdf | |
dc.type.qualificationlevel | Doctoral | |
dc.type.qualificationname | Ph.D | |