التفاصيل البيبلوغرافية
| العنوان: |
A FOXO-dependent replication checkpoint restricts proliferation of damaged cells |
| المؤلفون: |
Hornsveld, Marten, Feringa, Femke M., Krenning, Lenno, van den Berg, Jeroen, Smits, Lydia M.M., Nguyen, Nguyen B.T., Rodríguez-Colman, Maria J., Dansen, Tobias B., Medema, René H., Burgering, Boudewijn M.T. |
| المساهمون: |
CMM Groep Burgering, CMM Groep Rodriguez Colman, Cancer, CMM Groep Dansen, CMM Sectie Molecular Cancer Research |
| سنة النشر: |
2021 |
| مصطلحات موضوعية: |
cell cycle exit, checkpoint recovery, DNA damage checkpoint, DNA replication stress, EMI1, FOXO, genomic instability, senescence, General Biochemistry,Genetics and Molecular Biology |
| الوصف: |
DNA replication is challenged by numerous exogenous and endogenous factors that can interfere with the progression of replication forks. Substantial accumulation of single-stranded DNA during DNA replication activates the DNA replication stress checkpoint response that slows progression from S/G2 to M phase to protect genomic integrity. Whether and how mild replication stress restricts proliferation remains controversial. Here, we identify a cell cycle exit mechanism that prevents S/G2 phase arrested cells from undergoing mitosis after exposure to mild replication stress through premature activation of the anaphase promoting complex/cyclosome (APC/CCDH1). We find that replication stress causes a gradual decrease of the levels of the APC/CCDH1 inhibitor EMI1/FBXO5 through Forkhead box O (FOXO)-mediated inhibition of its transcription factor E2F1. By doing so, FOXOs limit the time during which the replication stress checkpoint is reversible and thereby play an important role in maintaining genomic stability. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
2211-1247 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/445680 |
| الاتاحة: |
https://dspace.library.uu.nl/handle/1874/445680 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.3743CC2A |
| قاعدة البيانات: |
BASE |
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