1 Ocak 2022 Dergi makalesi Açık Erişim

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

MARC21 XML

<?xml version='1.0' encoding='UTF-8'?>
<record xmlns="http://www.loc.gov/MARC21/slim">
  <leader>00000nam##2200000uu#4500</leader>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Camur, Bilge Bahar</subfield>
    <subfield code="u">Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Gul, Seref</subfield>
    <subfield code="u">Istanbul Univ, Dept Biol, Biotechnol Div, Istanbul, Turkey</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Ozcan, Onur</subfield>
    <subfield code="u">Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Baris, Ibrahim</subfield>
    <subfield code="u">Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</subfield>
  </datafield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Kavakli, Ibrahim Halil</subfield>
  </datafield>
  <datafield tag="909" ind1="C" ind2="4">
    <subfield code="p">JOURNAL OF BIOLOGICAL CHEMISTRY</subfield>
    <subfield code="v">298</subfield>
    <subfield code="n">9</subfield>
  </datafield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">user-tubitak-destekli-proje-yayinlari</subfield>
  </datafield>
  <datafield tag="540" ind1=" " ind2=" ">
    <subfield code="a">Creative Commons Attribution</subfield>
    <subfield code="u">http://www.opendefinition.org/licenses/cc-by</subfield>
  </datafield>
  <datafield tag="024" ind1=" " ind2=" ">
    <subfield code="a">10.1016/j.jbc.2022.102334</subfield>
    <subfield code="2">doi</subfield>
  </datafield>
  <datafield tag="245" ind1=" " ind2=" ">
    <subfield code="a">The secondary pocket of cryptochrome 2 is important for the regulation of its stability and localization</subfield>
  </datafield>
  <datafield tag="100" ind1=" " ind2=" ">
    <subfield code="a">Parlak, Gizem Cagla</subfield>
    <subfield code="u">Koc Univ, Dept Mol Biol &amp; Genet, Istanbul, Turkey</subfield>
  </datafield>
  <datafield tag="909" ind1="C" ind2="O">
    <subfield code="o">oai:aperta.ulakbim.gov.tr:258591</subfield>
    <subfield code="p">user-tubitak-destekli-proje-yayinlari</subfield>
  </datafield>
  <datafield tag="650" ind1="1" ind2="7">
    <subfield code="2">opendefinition.org</subfield>
    <subfield code="a">cc-by</subfield>
  </datafield>
  <datafield tag="260" ind1=" " ind2=" ">
    <subfield code="c">2022-01-01</subfield>
  </datafield>
  <datafield tag="856" ind1="4" ind2=" ">
    <subfield code="u">https://aperta.ulakbim.gov.trrecord/258591/files/bib-414de85d-c8c4-4862-a46d-98d1c75736b7.txt</subfield>
    <subfield code="z">md5:171def43d85c2da0578fb8e01f6a2844</subfield>
    <subfield code="s">221</subfield>
  </datafield>
  <datafield tag="542" ind1=" " ind2=" ">
    <subfield code="l">open</subfield>
  </datafield>
  <controlfield tag="005">20230729081119.0</controlfield>
  <controlfield tag="001">258591</controlfield>
  <datafield tag="980" ind1=" " ind2=" ">
    <subfield code="a">publication</subfield>
    <subfield code="b">article</subfield>
  </datafield>
  <datafield tag="520" ind1=" " ind2=" ">
    <subfield code="a">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.</subfield>
  </datafield>
</record>