Genetic and Physical Interactions Between DPB11 and DDC1 in the Yeast DNA Damage Response Pathway
Abstract
DPB11 is essential for DNA replication and S/M checkpoint control in Saccharomyces cerevisiae. The Dpb11 protein contains four BRCT domains, which have been proposed to be involved in protein-protein interactions. To further investigate the regulation and function of Dpb11, a yeast two-hybrid screen was carried out to identify proteins that physically interact with Dpb11. One positive clone isolated from the screen encoded a carboxyl-terminal fragment of Ddc1 (339–612 aa). Ddc1 is a DNA damage checkpoint protein, which, together with Mec3 and Rad17, has been proposed to form a PCNA-like complex and acts upstream in the DNA damage checkpoint pathways. We further determined that the carboxyl region of Dpb11 is required for its interaction with Ddc1. DDC1 and DPB11 also interact genetically. The Δddc1 dpb11-1 double mutant is more UV and MMS sensitive than the Δddc1 or the dpb11-1 single mutants. Furthermore, the double mutant is more hydroxyurea sensitive and displayed a lower restrictive temperature than dpb11-1. These results suggest that DPB11 and DDC1 may function in the same or parallel pathways after DNA damage and that DDC1 may play a role in responding to replication defects.
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In S. cerevisiae, Mec1 can be activated by Ddc1 and by Dpb11 recruited through Ddc1.
“In S. cerevisiae the Mec1 apical kinase can be activated both by the Ddc1 subunit of the checkpoint clamp and by the adaptor protein Dpb11 which is recruited at the lesion through interaction with Ddc1 [19–23].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [20]
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- Authors
- Wang, H., & Elledge, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Elledge, Stephen J
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-04-01
- Volume
- 160
- Issue
- 4
- Pages
- 1295-1304
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2145164509
- Cited by
- 79
- References
- 45
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-44664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Dpb11, DNA damage response, Saccharomyces cerevisiae, BRCT domain, protein-protein interaction, DNA replication checkpoint, Rad17, UV sensitivity, MMS sensitivity, hydroxyurea sensitivity, temperature-sensitive mutants, genetic interactions
- MeSH terms
- DNA Repair, DNA, Fungal, Phosphoproteins, Saccharomyces cerevisiae, Cell Cycle Proteins, Two-Hybrid System Techniques, Saccharomyces cerevisiae Proteins, In Vitro Techniques
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