A role for homologous recombination proteins in cell cycle regulation.

Détails

ID Serval
serval:BIB_677D328C43ED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A role for homologous recombination proteins in cell cycle regulation.
Périodique
Cell Cycle
Auteur(s)
Kostyrko K., Bosshard S., Urban Z., Mermod N.
ISSN
1551-4005 (Electronic)
ISSN-L
1551-4005
Statut éditorial
Publié
Date de publication
2015
Volume
14
Numéro
17
Pages
2853-2861
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Eukaryotic cells respond to DNA breaks, especially double-stranded breaks (DSBs), by activating the DNA damage response (DDR), which encompasses DNA repair and cell cycle checkpoint signaling. The DNA damage signal is transmitted to the checkpoint machinery by a network of specialized DNA damage-recognizing and signal-transducing molecules. However, recent evidence suggests that DNA repair proteins themselves may also directly contribute to the checkpoint control. Here, we investigated the role of homologous recombination (HR) proteins in normal cell cycle regulation in the absence of exogenous DNA damage. For this purpose, we used Chinese Hamster Ovary (CHO) cells expressing the Fluorescent ubiquitination-based cell cycle indicators (Fucci). Systematic siRNA-mediated knockdown of HR genes in these cells demonstrated that the lack of several of these factors alters cell cycle distribution, albeit differentially. The knock-down of MDC1, Rad51 and Brca1 caused the cells to arrest in the G2 phase, suggesting that they may be required for the G2/M transition. In contrast, inhibition of the other HR factors, including several Rad51 paralogs and Rad50, led to the arrest in the G1/G0 phase. Moreover, reduced expression of Rad51B, Rad51C, CtIP and Rad50 induced entry into a quiescent G0-like phase. In conclusion, the lack of many HR factors may lead to cell cycle checkpoint activation, even in the absence of exogenous DNA damage, indicating that these proteins may play an essential role both in DNA repair and checkpoint signaling.
Mots-clé
Animals, CHO Cells, Cell Cycle/physiology, Cell Cycle Proteins/physiology, Cricetinae, Cricetulus, Homologous Recombination/physiology, Humans, Recombinant Proteins
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/01/2016 11:24
Dernière modification de la notice
20/08/2019 14:23
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