1 Ocak 2022 Dergi makalesi Açık Erişim

Parlak, Gizem Cagla; Camur, Bilge Bahar; Gul, Seref; Ozcan, Onur; Baris, Ibrahim; Kavakli, Ibrahim Halil

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/258591</identifier>
  <creators>
    <creator>
      <creatorName>Parlak, Gizem Cagla</creatorName>
      <givenName>Gizem Cagla</givenName>
      <familyName>Parlak</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Camur, Bilge Bahar</creatorName>
      <givenName>Bilge Bahar</givenName>
      <familyName>Camur</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Gul, Seref</creatorName>
      <givenName>Seref</givenName>
      <familyName>Gul</familyName>
      <affiliation>Istanbul Univ, Dept Biol, Biotechnol Div, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Ozcan, Onur</creatorName>
      <givenName>Onur</givenName>
      <familyName>Ozcan</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Baris, Ibrahim</creatorName>
      <givenName>Ibrahim</givenName>
      <familyName>Baris</familyName>
      <affiliation>Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Kavakli, Ibrahim Halil</creatorName>
      <givenName>Ibrahim Halil</givenName>
      <familyName>Kavakli</familyName>
    </creator>
  </creators>
  <titles>
    <title>The Secondary Pocket Of Cryptochrome 2 Is Important For The Regulation Of Its Stability And Localization</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2022</publicationYear>
  <dates>
    <date dateType="Issued">2022-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/258591</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.jbc.2022.102334</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Human clock-gene variations contribute to the phenotypic differences observed in various behavioral and physiological processes, such as diurnal preference, sleep, metabolism, mood regulation, addiction, and fertility. However, little is known about the possible effects of identified variations at the molecular level. In this study, we performed a functional characterization at the cellular level of rare cryptochrome 2 (CRY2) missense variations that were identified from the Ensembl database. Our structural studies revealed that three variations (p.Pro123Leu, p.Asp406His, and p.Ser410Ile) are located at the rim of the secondary pocket of CRY2. We show that these variants were unable to repress CLOCK (circadian locomotor output cycles kaput)/BMAL1 (brain and muscle ARNT-like-1)-driven transcription in a cell-based reporter assay and had reduced affinity to CLOCK-BMAL1. Furthermore, our biochemical studies indicated that the variants were less stable than the WT CRY2, which could be rescued in the presence of period 2 (PER2), another core clock protein. Finally, we found that these variants were unable to properly localize to the nucleus and thereby were unable to rescue the circadian rhythm in a Cry1(-/-)Cry2(-/-) double KO mouse embryonic fibroblast cell line. Collectively, our data suggest that the rim of the secondary pocket of CRY2 plays a significant role in its nuclear localization independently of PER2 and in the intact circadian rhythm at the cellular level.</description>
  </descriptions>
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