The DNA replication checkpoint (DRC) and the DNA damage checkpoint (DDC) are two closely linked signaling cascades that adjust S phase to the presence of DNA lesions and other replication impediments. Two recent studies published in The EMBO Journal shed new light on their relationship in budding yeast, collectively showing that the two pathways—while sharing several factors—differ in the location and kinetics of their activation, suggesting that they constitute different branches of an integrated cellular response to impaired DNA replication.
See also: J Bacal et al and N García-Rodríguez et al
Genome stability is threatened during S phase, when DNA lesions and other impediments to DNA replication impair the faithful duplication of the genetic information. Therefore, DNA replication is safeguarded by two separable, but related mechanisms termed DNA replication checkpoint and intra‐S phase DNA damage checkpoint (Branzei & Foiani, 2009). These checkpoint pathways represent conserved phosphorylation‐based signaling cascades, which trigger both local and cell‐wide responses to the presence of DNA damage and replication perturbation. Interestingly, DRC and DDC share several essential components, such as the sensor kinase (Mec1‐Ddc2, budding yeast homologs of mammalian ATR‐ATRIP) and the effector kinase (Rad53 in budding yeast), but are defined by the mutually exclusive involvement of specific mediator proteins, yeast Mrc1 (DRC) and Rad9 (DDC).
Since the discovery of Mrc1 and Rad9, the relationship between DRC and DDC has been intensely studied (summarized in Branzei & Foiani, 2009) leading to a picture that appears contradictory at first glance. On the one hand, DRC and DDC are thought to react to different signals, stalled replication forks, and DNA lesions, respectively, …
Subscribers, please sign in with your username and password.
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
EMBO Members please login here to access the journals
Subscribe to the Journal
Recommend to your Librarian
