Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint

Abstract

ATR is a replication-dependent chromatin-binding protein, and its association with chromatin is dependent on RNA synthesis by DNA polymerase alpha. Depletion of ATR leads to premature mitosis in the presence and absence of aphidicolin, indicating that ATR is required for the DNA replication checkpoint.

Replication stress activates DNA polymerase alpha-associated Chk1

“…[28][29][30]44,45 Chk1 can be phosphorylated on Ser 317 and 345 by ATR in response to stalled replication forks. 28,29,46 We next examined the relative contribution of ATR and ATM to Chk1 activation following replication stress, by analyzing the epistatic relationship between Chk1, ATR and ATM, following Polα depletion.…”

An Overactivated ATR/CHK1 Pathway Is Responsible for the Prolonged G2 Accumulation in Irradiated AT Cells

“…The fact of ATM-regulated S and G 2 -M checkpoints in a dose (IR)-dependent manner is supported more by the model of combined trans-and cis-acting processes. ATR is also a DNA binding protein (54,55). In the absence of ATM, ATR may have a greater opportunity to interact directly with the damaged DNA induced by IR and cause the observed overactivation.…”

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

“…It has been shown that Xenopus egg extract can reproduce several aspects of DNA damage response and has provided significant insights into checkpoint mechanisms (Costanzo et al, 2000;Costanzo et al, 2003). Importantly, ATM/ATR have been isolated and found to function in regulating DNA damage checkpoint pathways within Xenopus egg extract (Robertson et al, 1999;Costanzo et al, 2000;Hekmat-Nejad et al, 2000;. In using this system, chemicals can be added to interfere with biochemical processes.…”