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An Investigation of Microtubule-Kinetochore Attachment Mechanisms
An Investigation of Microtubule-Kinetochore Attachment Mechanisms
An Investigation of Microtubule-Kinetochore Attachment Mechanisms

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자료유형  
 학위논문 서양
최종처리일시  
20250211151028
ISBN  
9798382215389
DDC  
574.191
저자명  
Murray, Lucas Edward.
서명/저자  
An Investigation of Microtubule-Kinetochore Attachment Mechanisms
발행사항  
[Sl] : University of Washington, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
126 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-10, Section: B.
주기사항  
Advisor: Asbury, Chip.
학위논문주기  
Thesis (Ph.D.)--University of Washington, 2024.
초록/해제  
요약The ability to replicate is a defining feature of life. At the center of eukaryotic cell division are a set of protein machines responsible for pulling apart the chromosomes before cells divide. Spindle microtubules grow from the poles of the cell and connect to chromosomes via protein complexes called kinetochores. Kinetochores must maintain tenacious attachments to microtubule tips, even as they assemble and disassemble underneath their grip. Additionally, kinetochores mediate an error correction process to ensure the proper attachments to microtubules are formed before separation of the chromosomes commences. Here, I work to understand how the proteins in the kinetochore work together to maintain attachments to microtubules. I investigate two different mechanisms for microtubule-kinetochore attachment: the conformational wave mechanism and the biased diffusion mechanism. I developed a new optical trapping assay, using it to show that microtubule protofilament morphological and energetic properties can be measured and changed. I investigate the role of protofilament curl enlargement in the attachment and motility of the kinetochore. I develop theoretical models that show that the biased diffusion mechanism can fit experimentally measured detachment rates for assembling and disassembling kinetochores. Finally, I show kinetochores exhibit asymmetry in their sliding friction when they are dragged along microtubule lattices, a new phenomenon for microtubule-kinetochore biophysics. I argue this sliding friction forms the basis for a new mode of error correction during cell division, one that likely holds across most eukaryotic organisms.
일반주제명  
Biophysics
일반주제명  
Physiology
일반주제명  
Cellular biology
일반주제명  
Morphology
키워드  
Cell division
키워드  
Kinetochores
키워드  
Microtubules
키워드  
Mitosis
키워드  
Optical trapping
기타저자  
University of Washington Physiology and Biophysics
기본자료저록  
Dissertations Abstracts International. 85-10B.
전자적 위치 및 접속  
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MARC

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■0820  ▼a574.191
■1001  ▼aMurray,  Lucas  Edward.
■24513▼aAn  Investigation  of  Microtubule-Kinetochore  Attachment  Mechanisms
■260    ▼a[Sl]▼bUniversity  of  Washington▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a126  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-10,  Section:  B.
■500    ▼aAdvisor:  Asbury,  Chip.
■5021  ▼aThesis  (Ph.D.)--University  of  Washington,  2024.
■520    ▼aThe  ability  to  replicate  is  a  defining  feature  of  life.  At  the  center  of  eukaryotic  cell  division  are  a  set  of  protein  machines  responsible  for  pulling  apart  the  chromosomes  before  cells  divide.  Spindle  microtubules  grow  from  the  poles  of  the  cell  and  connect  to  chromosomes  via  protein  complexes  called  kinetochores.  Kinetochores  must  maintain  tenacious  attachments  to  microtubule  tips,  even  as  they  assemble  and  disassemble  underneath  their  grip.  Additionally,  kinetochores  mediate  an  error  correction  process  to  ensure  the  proper  attachments  to  microtubules  are  formed  before  separation  of  the  chromosomes  commences.  Here,  I  work  to  understand  how  the  proteins  in  the  kinetochore  work  together  to  maintain  attachments  to  microtubules.  I  investigate  two  different  mechanisms  for  microtubule-kinetochore  attachment:  the  conformational  wave  mechanism  and  the  biased  diffusion  mechanism.  I  developed  a  new  optical  trapping  assay,  using  it  to  show  that  microtubule  protofilament  morphological  and  energetic  properties  can  be  measured  and  changed.  I  investigate  the  role  of  protofilament  curl  enlargement  in  the  attachment  and  motility  of  the  kinetochore.  I  develop  theoretical  models  that  show  that  the  biased  diffusion  mechanism  can  fit  experimentally  measured  detachment  rates  for  assembling  and  disassembling  kinetochores.  Finally,  I  show  kinetochores  exhibit  asymmetry  in  their  sliding  friction  when  they  are  dragged  along  microtubule  lattices,  a  new  phenomenon  for  microtubule-kinetochore  biophysics.  I  argue  this  sliding  friction  forms  the  basis  for  a  new  mode  of  error  correction  during  cell  division,  one  that  likely  holds  across  most  eukaryotic  organisms.
■590    ▼aSchool  code:  0250.
■650  4▼aBiophysics
■650  4▼aPhysiology
■650  4▼aCellular  biology
■650  4▼aMorphology
■653    ▼aCell  division
■653    ▼aKinetochores
■653    ▼aMicrotubules
■653    ▼aMitosis
■653    ▼aOptical  trapping
■690    ▼a0786
■690    ▼a0379
■690    ▼a0287
■690    ▼a0719
■71020▼aUniversity  of  Washington▼bPhysiology  and  Biophysics.
■7730  ▼tDissertations  Abstracts  International▼g85-10B.
■790    ▼a0250
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160490▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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