FACT is heterodimer protein complex and histone chaperone that plays an important role in maintaining and modifying chromatin structure during various DNA-dependent processes. FACT is involved in nucleosome assembly de novo and in the preservation and recovery of the nucleosome structure during and after transcription, replication and repair of DNA. During transcript elongation FACT reduces the height of the nucleosome barrier and supports survival of the nucleosomes during and after passage of RNA polymerase II. In this process FACT interacts with histone H2A-H2B dimer in nucleosomes, thus facilitating uncoiling of nucleosomal DNA from the octamer of histones; it also facilitates subsequent recovery of the canonical structure of the nucleosome after transcription. FACT also plays an important role in transformation of human cells and in maintaining the viability of the tumor cells.
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http://dx.doi.org/10.7868/S0026898415060026 | DOI Listing |
Front Med
January 2025
Guizhou University Medical College, Guiyang, 550025, China.
The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Triple-negative breast cancer (TNBC) is a difficulty and bottleneck in the clinical treatment of breast cancer due to a lack of effective therapeutic targets. Herein, we first report that secernin 2 (SCRN2), an uncharacterized gene in human cancer, acts as a novel tumor suppressor in TNBC to inhibit cancer progression and enhance therapeutic sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition both in vitro and in vivo. SCRN2 is downregulated in TNBC through chaperone-mediated autophagic degradation, and its downregulation is associated with poor patient prognosis.
View Article and Find Full Text PDFEMBO J
January 2025
Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo.
View Article and Find Full Text PDFbioRxiv
November 2024
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
To maintain genome stability, proliferating cells must enact a program of telomere maintenance. While most tumors maintain telomeres through the action of telomerase, a subset of tumors utilize a DNA-templated process termed Alternative Lengthening of Telomeres or ALT. ALT is associated with mutations in the ATRX/DAXX/H3.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Brain damage induced by ischemia promotes the development of cognitive dysfunction, thus increasing the risk of dementia such as Alzheimer's disease (AD). Studies indicate that cellular acidification-triggered activation of asparagine endopeptidase (AEP) plays a key role in ischemic brain injury, through multiple molecular pathways, including cleavage of its substrates such as SET (inhibitor 2 of PP2A, I ) and Tau. However, whether direct targeting AEP can effectively prevent post-stroke cognitive impairment (PSCI) remains unanswered.
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