DNA Replication Arrest and DNA Damage Responses Induced by Alkylating Minor Groove Binders
Abstract
We are interested in the molecular mechanisms involved in DNA replication arrest by the S phase DNA damage checkpoints. Using in vitro simian virus 40 DNA replication assays, we have found three factors that directly contribute to DNA damage-induced DNA replication arrest: Replication Protein A (RPA), DNA-dependent protein kinase (DNA-PK), and a yet to be identified replication inhibitor. Both DNA-PK and the unknown factor are functioned as trans-acting inhibitors. RPA is the major eukaryotic single-stranded DNA binding protein required for DNA replication, repair and recombination. Upon DNA damage, RPA is found hyperphosphorylated and redistributed within nuclei to form foci. These two events require the replication fork movement under certain DNA damaging agent treatments. However, there is also a replication-independent mechanism associated with the actions of some DNA damaging agents. We hypothesize that the requirement of on-going DNA replication to induce RPA modification and foci formation is dependent on types of DNA lesion. Our results also suggest that RPA could be used as a cellular DNA damage marker to study the actions of chemotherapeutic agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA392506
Entities
People
- Shue-ru Kuo
- Thomas Melendy
Organizations
- University at Buffalo