Pichierri Pietro, Ammazzalorso Francesca, Bignami Margherita, Franchitto Annapaola
Genome stability group, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
Aging (Albany NY). 2011 Mar;3(3):311-8. doi: 10.18632/aging.100293.
The Werner syndrome protein (WRN) is a member of the human RecQ family DNA helicases implicated in the maintenance of genome stability. Loss of WRN gives rise to the Werner syndrome, a genetic disease characterised by premature aging and cancer predisposition. WRN plays a crucial role in the response to replication stress and significantly contributes to the recovery of stalled replication forks, although how this function is regulated is not fully appreciated. There is a growing body of evidence that WRN accomplishes its task in close connection with the replication checkpoint. In eukaryotic cells, the replication checkpoint response, which involves both the ATR and ATM kinase activities, is deputed to the maintenance of fork integrity and re-establishment of fork progression. Our recent findings indicate that ATR and ATM modulate WRN function at defined steps of the response to replication fork arrest. This review focuses on the novel evidence of a functional relationship between WRN and the replication checkpoint and how this cross-talk might contribute to prevent genome instability, a common feature of senescent and cancer cells.
沃纳综合征蛋白（WRN）是人类RecQ家族DNA解旋酶的成员之一，与基因组稳定性的维持有关。WRN的缺失会导致沃纳综合征，这是一种以早衰和癌症易感性为特征的遗传疾病。WRN在应对复制应激中起着关键作用，并对停滞的复制叉的恢复有显著贡献，尽管这种功能是如何被调控的尚未完全明确。越来越多的证据表明，WRN是与复制检查点密切相关来完成其任务的。在真核细胞中，涉及ATR和ATM激酶活性的复制检查点反应负责维持叉状结构的完整性和重新建立叉状结构的进展。我们最近的研究结果表明，ATR和ATM在对复制叉停滞的反应的特定步骤中调节WRN功能。这篇综述重点关注WRN与复制检查点之间功能关系的新证据，以及这种相互作用如何可能有助于预防基因组不稳定，这是衰老细胞和癌细胞的一个共同特征。
