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Understanding the Role of DNA Discontinuities in Promoting Meiotic Crossing Over
Understanding the Role of DNA Discontinuities in Promoting Meiotic Crossing Over
Understanding the Role of DNA Discontinuities in Promoting Meiotic Crossing Over

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211152644
ISBN  
9798384051053
DDC  
574
저자명  
Payero, Lisette.
서명/저자  
Understanding the Role of DNA Discontinuities in Promoting Meiotic Crossing Over
발행사항  
[Sl] : Cornell University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
179 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
주기사항  
Advisor: Alani, Eric.
학위논문주기  
Thesis (Ph.D.)--Cornell University, 2024.
초록/해제  
요약Meiosis is a specialized form of cell division that results in the formation of gametes. In most sexually reproducing organisms, meiotic recombination is a crucial step in meiosis during which homologous chromosomes physically interact and exchange genetic information. The final DNA recombination intermediate in this process is the double Holliday Junction (dHJ). A major question in the meiosis field is the mechanism through which dHJs are cleaved in a biased manner to create crossover products. Mlh1-Mlh3, the nuclease responsible for resolving the majority of dHJs in budding yeast, is not intrinsically capable of recognizing and cleaving dHJs in a biased manner. This observation, combined with genetic screens revealing a wide variety of crossover promoting factors, indicates that other proteins may interact at the dHJ to promote biased resolution. Here, I describe work demonstrating genetic evidence in baker's yeast that the Rad2/XPG family nuclease Exo1 promotes meiotic crossing over by protecting DNA nicks from ligation. I describe findings that structural elements in Exo1 that interact with DNA, such as those required for the bending of DNA during nick/flap recognition, are critical for its role in crossing over. In addition, meiotic overexpression of Cdc9 ligase reduces the crossover levels of exo1 DNA-binding mutants to levels that approach the exo1 null. I synthesize these observations to propose a model in which temporally protected, dHJ-associated nicks are key features of biased resolution. Finally, I describe a novel technique for mapping meiotic DNA nicks genome-wide in wild-type, exo1Δ, and other mutant yeast strains. Using these data, I will interrogate existing models for crossover resolution and provide valuable insight into the structure of meiotic dHJs.
일반주제명  
Biochemistry
일반주제명  
Cellular biology
일반주제명  
Molecular biology
일반주제명  
Genetics
키워드  
Meiosis
키워드  
Double Holliday Junction
키워드  
Meiotic crossing over
키워드  
Chromosomes
키워드  
Meiotic recombination
기타저자  
Cornell University Biochemistry Molecular and Cell Biology
기본자료저록  
Dissertations Abstracts International. 86-03B.
전자적 위치 및 접속  
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■020    ▼a9798384051053
■035    ▼a(MiAaPQ)AAI31485585
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574
■1001  ▼aPayero,  Lisette.▼0(orcid)0000-0002-5919-5928
■24510▼aUnderstanding  the  Role  of  DNA  Discontinuities  in  Promoting  Meiotic  Crossing  Over
■260    ▼a[Sl]▼bCornell  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a179  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-03,  Section:  B.
■500    ▼aAdvisor:  Alani,  Eric.
■5021  ▼aThesis  (Ph.D.)--Cornell  University,  2024.
■520    ▼aMeiosis  is  a  specialized  form  of  cell  division  that  results  in  the  formation  of  gametes.  In  most  sexually  reproducing  organisms,  meiotic  recombination  is  a  crucial  step  in  meiosis  during  which  homologous  chromosomes  physically  interact  and  exchange  genetic  information.  The  final  DNA  recombination  intermediate  in  this  process  is  the  double  Holliday  Junction  (dHJ).  A  major  question  in  the  meiosis  field  is  the  mechanism  through  which  dHJs  are  cleaved  in  a  biased  manner  to  create  crossover  products.  Mlh1-Mlh3,  the  nuclease  responsible  for  resolving  the  majority  of  dHJs  in  budding  yeast,  is  not  intrinsically  capable  of  recognizing  and  cleaving  dHJs  in  a  biased  manner.  This  observation,  combined  with  genetic  screens  revealing  a  wide  variety  of  crossover  promoting  factors,  indicates  that  other  proteins  may  interact  at  the  dHJ  to  promote  biased  resolution.  Here,  I  describe  work  demonstrating  genetic  evidence  in  baker's  yeast  that  the  Rad2/XPG  family  nuclease  Exo1  promotes  meiotic  crossing  over  by  protecting  DNA  nicks  from  ligation.  I  describe  findings  that  structural  elements  in  Exo1  that  interact  with  DNA,  such  as  those  required  for  the  bending  of  DNA  during  nick/flap  recognition,  are  critical  for  its  role  in  crossing  over.  In  addition,  meiotic  overexpression  of  Cdc9  ligase  reduces  the  crossover  levels  of  exo1  DNA-binding  mutants  to  levels  that  approach  the  exo1  null.  I  synthesize  these  observations  to  propose  a  model  in  which  temporally  protected,  dHJ-associated  nicks  are  key  features  of  biased  resolution.  Finally,  I  describe  a  novel  technique  for  mapping  meiotic  DNA  nicks  genome-wide  in  wild-type,  exo1Δ,  and  other  mutant  yeast  strains.  Using  these  data,  I  will  interrogate  existing  models  for  crossover  resolution  and  provide  valuable  insight  into  the  structure  of  meiotic  dHJs.
■590    ▼aSchool  code:  0058.
■650  4▼aBiochemistry
■650  4▼aCellular  biology
■650  4▼aMolecular  biology
■650  4▼aGenetics
■653    ▼aMeiosis
■653    ▼aDouble  Holliday  Junction
■653    ▼aMeiotic  crossing  over
■653    ▼aChromosomes
■653    ▼aMeiotic  recombination
■690    ▼a0487
■690    ▼a0379
■690    ▼a0369
■690    ▼a0307
■71020▼aCornell  University▼bBiochemistry,  Molecular  and  Cell  Biology.
■7730  ▼tDissertations  Abstracts  International▼g86-03B.
■790    ▼a0058
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163251▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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