Molecular mechanisms of DNA replication checkpoint activation.
The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress) results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.
Institute of Human Genetics, CNRS-UPR1142, Department "Molecular Bases of Human Diseases", 141, Rue de la Cardonille, Montpellier 34396 Cedex 5, France. benedicterecolin@hotmail.com.
Bénédicte
B
Recolin
Institute of Human Genetics, CNRS-UPR1142, Department "Molecular Bases of Human Diseases", 141, Rue de la Cardonille, Montpellier 34396 Cedex 5, France. siem.vanderlaan@igh.cnrs.fr.
Siem
S
van der Laan
RNA Biogenesis Laboratory, Institute of Molecular Genetics of Montpellier, 1919 Route de Mende, Montpellier 34293, France. nikolay.tsanov@igmm.cnrs.fr.
Nikolay
N
Tsanov
Institute of Human Genetics, CNRS-UPR1142, Department "Molecular Bases of Human Diseases", 141, Rue de la Cardonille, Montpellier 34396 Cedex 5, France. domenico.maiorano@igh.cnrs.fr.
Domenico
D
Maiorano