Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase.

Dart, D; Adams, K; Akerman, I; Lakin, N

Journal article

Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase.

Abstract:: The ataxia telangiectasia-mutated (ATM) and Rad3-related kinase (ATR) is a central component of the cell cycle checkpoint machinery required to induce cell cycle arrest in response to DNA damage. Accumulating evidence suggests a role for ATR in signaling DNA damage during S-phase. Here we show that ATR is recruited to nuclear foci induced by replication fork stalling in a manner that is dependent on the single stranded binding protein replication protein A (RPA). ATR associates with chromatin in asynchronous cell cultures, and we use a variety of approaches to examine the association of ATR with chromatin in the absence of agents that cause genotoxic stress. Under our experimental conditions, ATR exhibits a decreased affinity for chromatin in quiescent cells and cells synchronized at mitosis but an increased affinity for chromatin as cells re-enter the cell cycle. Using centrifugal elutriation to obtain cells enriched at various stages of the cell cycle, we show that ATR associates with chromatin in a cell cycle-dependent manner, specifically during S-phase. Cell cycle association of ATR with chromatin mirrors that of RPA in addition to claspin, a cell cycle checkpoint protein previously shown to be a component of the replication machinery. Furthermore, association of ATR with chromatin occurs in the absence of detectable DNA damage and cell cycle checkpoint activation. These data are consistent with a model whereby ATR is recruited to chromatin during the unperturbed cell cycle and points to a role of ATR in monitoring genome integrity during normal S-phase progression.

Publication status:: Published

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APA Style

Dart, D., Adams, K., Akerman, I., & Lakin, N. (2004). Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase. Journal of Biological Chemistry, 279(16), 16433–16440.

MLA Style

Dart, D., et al. “Recruitment of the Cell Cycle Checkpoint Kinase ATR to Chromatin during S-Phase.” Journal of Biological Chemistry, vol. 279, no. 16, 2004, pp. 16433–40.

Chicago Style

Dart, D, K Adams, I Akerman, and N Lakin. 2004. “Recruitment of the Cell Cycle Checkpoint Kinase ATR to Chromatin during S-Phase.” Journal of Biological Chemistry 279 (16): 16433–40.
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