Interplay between wrn and the checkpoint in s-phase.
Stability of the genome is crucial for survival and faithful transmission of the genetic blueprint to progenitors. During DNA replication chromosome integrity can be challenged by a variety of exogenous and endogenous damaging agents and by the process of duplication itself. Thus, eukaryotic cells have evolved a sophisticated response called replication checkpoint supervising the accurate and complete genome replication. The replication checkpoint response bridges together replication, repair and cell cycle proteins in a coordinated network having the ATR kinase as culprit. ATR-mediated phosphorylation events control that stalled replication forks are properly sensed and stabilised, cell cycle progression halted and replication eventually recovered. In the recent years, the Werner syndrome protein (WRN) emerged as a central actor of the replication checkpoint being instrumental for correct recovery from arrested replication and a substrate of ATR. In this review, how WRN and the replication checkpoint could cross-talk and contribute to faithful recovery of stalled replication forks will be discussed.
Pichierri
Pietro
P
Genome Stability group at Section of Experimental and Computational Carcinogenesis, Istituto Superiore di Sanità, Rome, Italy. pietro.pichierri@iss.it
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D019143:Evolution, Molecular; D005090:Exodeoxyribonucleases; D015894:Genome, Human / Q000502:physiology*; D042822:Genomic Instability / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*; D000071657:Werner Syndrome Helicase
D018797:Cell Cycle Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase