کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5508731 1400396 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TRF2 recruits ORC through TRFH domain dimerization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
TRF2 recruits ORC through TRFH domain dimerization
چکیده انگلیسی


- TRF2 is thought to mediate ORC recruitment to the telomeric replication origins.
- Tethering of TRF2 by LacI fusion to a lacO array induces ORC recruitment.
- The TRFH domain of TRF2 is sufficient to recruit ORC and pre-RC onto the lacO array.
- The recruitment of ORC and pre-RC is dependent on dimerization of the TRFH domain.
- Dimerized TRFH domain binds to ORC via a direct interaction with the ORC1 subunit.

Telomeres are specialized chromatin structures that prevent the degradation and instability of the ends of linear chromosomes. While telomerase maintains long stretches of the telomeric repeat, the majority of telomeric DNA is duplicated by conventional DNA replication. A fundamental step in eukaryotic DNA replication involves chromatin binding of the origin recognition complex (ORC). In human cells, telomeric repeat binding factor 2 (TRF2) is thought to play a role in the recruitment of ORC onto telomeres. To better understand the mechanism of TRF2-mediated ORC recruitment, we utilized a lacO-LacI protein tethering system in U2OS cells and found that ectopically targeted TRF2, but not TRF1, can recruit ORC onto the lacO array. We further found that the TRF homology (TRFH) dimerization domain of TRF2, but not its mutant defective in dimerization, is sufficient for ORC and minichromosome maintenance (MCM) recruitment. Mutations impairing the dimerization also compromised ORC recruitment by full-length TRF2. Similar results were obtained using immunoprecipitation and GST pull-down assays. Together, these results suggest that dimerized TRF2 recruits ORC and stimulates pre-replication complex (pre-RC) formation at telomeres through the TRFH domain.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1864, Issue 1, January 2017, Pages 191-201
نویسندگان
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