Collision between a topoisomerase I-DNA intermediate and an advancing replication fork represents a unique form of replicative damage. We have shown previously that yeast H2A serine 129 is involved in the recovery from this type of damage. We now report that efficient repair also requires proteins involved in chromatid cohesion: Csm3; Tof1; Mrc1, and Dcc1. Epistasis analysis defined several pathways involving these proteins. Csm3 and Tof1 function in a same pathway and downstream of H2A. In addition, the pathway involving H2A/Csm3/Tof1 is distinct from the pathways involving the Ctf8/Ctf18/Dcc1 complex, the Rad9 pathway, and another involving Mrc1. Our genetic studies suggest a role for H2A serine 129 in the establishment of specialized cohesion structure necessary for the normal repair of topoisomerase I-induced DNA damage.
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http://dx.doi.org/10.1534/genetics.105.046128 | DOI Listing |
Exp Ther Med
January 2025
Department of Oncology and Hematology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250001, P.R. China.
N-methyladenosine (m1A), a methylation of RNA, is gaining attention for its role in diverse biological processes. However, the potential roles of m1A regulatory-mediated methylation modifications in multiple myeloma (MM) remain unclear. The mRNA expression of m1A regulators in normal plasma (NP; n=9) and MM (n=174) bone marrow plasma cells was investigated and the m1A modification patterns of 559 MM samples based on the expression of 10 m1A-related regulatory genes were comprehensively evaluated.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli No17, Chaoyang District, Beijing 100021, China.
The phosphorylation of histone H2A.X into γH2A.X is a crucial early event in the DNA damage response, marking DNA damage sites and initiating repair processes.
View Article and Find Full Text PDFEpigenetics Chromatin
November 2024
Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.
Background: Bone remodeling is a continuous and balanced process which relies on the dynamic equilibrium between osteoclastic bone resorption and osteoblastic bone formation. During osteoclast differentiation, pro-osteoclastogenic and anti-osteoclastogenic genes are selectively targeted by positive and negative transcription regulators, respectively. VprBP, also known as DCAF1, is a recently identified kinase and plays an important role in driving epigenetic gene silencing and oncogenic transformation.
View Article and Find Full Text PDFGenetics
January 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Duke University, Durham, NC 27710, USA.
Near the C-terminus of histone H2A in the yeast Saccharomyces cerevisiae, there are 2 serines (S122 and S129) that are targets of phosphorylation. The phosphorylation of serine 129 in response to DNA damage is dependent on the Tel1 and Mec1 kinases. In Schizosaccharomyces pombe and S.
View Article and Find Full Text PDFPLoS Genet
October 2024
Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
The DNA damage response (DDR) constitutes a vital cellular process that safeguards genome integrity. This biological process involves substantial alterations in chromatin structure, commonly orchestrated by epigenetic enzymes. Here, we show that the epigenetic modifier N-terminal acetyltransferase 4 (Nat4), known to acetylate the alpha-amino group of serine 1 on histones H4 and H2A, is implicated in the response to DNA damage in S.
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