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- Title
A Dbf4p BRCA1 C-Terminal-Like Domain Required for the Response to Replication Fork Arrest in Budding Yeast.
- Authors
Gabrielse, Carrie; Miller, Charles T.; McConnell, Kristopher H.; Deward, Aaron; Fox, Catherine A.; Weinreich, Michael
- Abstract
Dbf4p is an essential regulatoiy subunit of the Cdc7p kinase required for the initiation of DNA replication. Cdc7p and Dbf4p orthologs have also been shown to function in the response to DNA damage. A previous Dbf4p multiple sequence alignment identified a conserved ∼40-residue N-terminal region with similarity to the BRGA1 G-terminal (BRCT) motif called ‘motif N.’ BRCT motifs encode ∼100-amino-acid domains involved in the DNA damage response. We have identified an expanded and conserved ∼100-residue N-terminal region of Dhf4p that includes motif N but is capable of encoding a single BRCT-like domain. Dhf4p orthologs diverge from the BRCT motif at the C terminus hut may encode a similar secondary structure in this region. We have therefore called this the BRCT and DBF4 similarity (BRDF) motif. The principal role of this Dbf4p motif was in the response to replication fork (RF) arrest; however, it was not required for cell cycle progression, activation of Cdc7p kinase activity, or interaction with the origin recognition complex (ORC) postulated to recruit Cdc7p-Dbf4p to origins. Rad53p likely directly phosphorylated Dhf4p in response to RF arrest and Dhf4p was required for Rad53p abundance. Rad53p and Dbf4p therefore cooperated to coordinate a robust cellular response to RF arrest.
- Subjects
DNA replication; YEAST; ASEXUAL reproduction; DNA synthesis; REPLICATION (Experimental design); GENETIC mutation
- Publication
Genetics, 2006, Vol 173, Issue 2, p541
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.106.057521