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Dissociation of Radiation-induced Phosphorylation of Replication Protein A from the S-Phase Checkpoint¹

The Johns Hopkins Oncology Center, Baltimore, Maryland 21205

Replication protein A (RPA) is a trimeric single-stranded DNA-binding protein complex involved in DNA replication, repair, and recombination. DNA damage induces phosphorylation of the RPA p34 subunit, and it has been speculated that this phosphorylation could contribute to the regulation of the DNA damage-induced S-phase checkpoint. To further examine this potential relationship, human cell lines expressing ataxia telangiectasia (AT)-mutated dominant-negative fragments, which fail to arrest in S phase in response to ionizing radiation (IR), and AT cells expressing AT-mutated-complementing fragments, which regain the ability to arrest replicative DNA synthesis in response to IR, were analyzed for radiation-induced RPA phosphorylation. Results from these studies demonstrate that IR-induced RPA phosphorylation can be uncoupled from the S-phase checkpoint, suggesting that RPA phosphorylation in response to IR is neither necessary nor sufficient for an S-phase arrest.

¹ This work was supported in part by NIH Grant CA71387. M. B. K. is the Steven Birnbaum Scholar of the Leukemia Society of America.

² To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center, Ross Building, Room 345, 720 Rutland Avenue, Baltimore, MD 21205. Phone: (410) 955-4967; Fax: (410) 614-4095; E-mail: mbkastan@welchlink.welch.jhu.edu.

Received 5/19/97. Accepted 7/ 2/97.

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