Abp1, and the closely related Cbh1 and Cbh2 are homologous to the human centromere-binding protein CENP-B that has been implicated in the assembly of centromeric heterochromatin. Fission yeast cells lacking Abp1 show an increase in mini-chromosome instability suggesting that Abp1 is important for chromosome segregation and/or DNA synthesis. Here we show that Abp1 interacts with the DNA replication protein Cdc23 (MCM10) in a two-hybrid assay, and that the Deltaabp1 mutant displays a synthetic phenotype with a cdc23 temperature-sensitive mutant. Moreover, genetic interactions were also observed between abp1+ and four additional DNA replication initiation genes cdc18+, cdc21+, orc1+, and orc2+. Interestingly, we find that S phase is delayed in cells deleted for abp1+ when released from a G1 block. However, no delay is observed when cells are released from an early S phase arrest induced by hydroxyurea suggesting that Abp1 functions prior to, or coincident with, the initiation of DNA replication.
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http://dx.doi.org/10.1186/1747-1028-1-27 | DOI Listing |
CNS Drugs
January 2025
School of Medicine and Dentistry, Gold Coast Campus, Griffith University, Southport, QLD, 4222, Australia.
Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.
View Article and Find Full Text PDFCells
December 2024
Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, 4100 John R Street, Detroit, MI 48201, USA.
The DNA replication machinery is highly conserved from bacteria to eukaryotic cells. Faithful DNA replication is vital for cells to transmit accurate genetic information to the next generation. However, both internal and external DNA damages threaten the intricate DNA replication process, leading to the activation of the DNA damage response (DDR) system.
View Article and Find Full Text PDFGenetics
January 2025
Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
Mismatch repair (MMR) is a highly conserved DNA repair pathway that recognizes mispairs that occur spontaneously during DNA replication and coordinates their repair. In Saccharomyces cerevisiae, Msh2-Msh3 and Msh2-Msh6 initiate MMR by recognizing and binding insertion deletion loops (in/dels) up to ∼ 17 nucleotides (nt.) and base-base mispairs, respectively; the two complexes have overlapping specificity for small (1-2 nt.
View Article and Find Full Text PDFGenes Cells
January 2025
Jiangsu Key Laboratory for Pathogens and Ecosystems, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Serine-arginine protein kinases (SRPKs) play important roles in diverse biological processes such as alternative splicing and cell cycle. However, the functions of SRPKs in DNA damage response remain unclear. Here we characterized the function of SRPKs homolog Dsk1 in regulating DNA repair in the fission yeast Schizosaccharomyces pombe.
View Article and Find Full Text PDFOrphanet J Rare Dis
December 2024
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background: Meier-Gorlin syndrome (MGORS) is a rare autosomal inherited form of primordial dwarfism. Pathogenic variants in 13 genes involved in DNA replication initiation have been identified in this disease, but homozygous intronic variants have never been reported. Additionally, whether growth hormone (GH) treatment can increase the height of children with MGORS is unclear.
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