ASF1A

Last update 08 May 2025

Basic Info

Synonyms

anti-silencing function 1A histone chaperone, Anti-silencing function protein 1 homolog A, ASF1A

+ [7]

Introduction

Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly (PubMed:10759893, PubMed:11897662, PubMed:12842904, PubMed:14718166, PubMed:15664198, PubMed:16151251, PubMed:21454524). Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly (PubMed:11897662, PubMed:14718166, PubMed:15664198). Promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks: acts by mediating histone replacement at DSBs, leading to recruitment of the MMS22L-TONSL complex and subsequent loading of RAD51 (PubMed:29478807). Also involved in the nuclear import of the histone H3-H4 dimer together with importin-4 (IPO4): specifically recognizes and binds newly synthesized histones with the monomethylation of H3 'Lys-9' and acetylation at 'Lys-14' (H3K9me1K14ac) marks, and diacetylation at 'Lys-5' and 'Lys-12' of H4 (H4K5K12ac) marks in the cytosol (PubMed:21454524, PubMed:29408485). Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit (PubMed:15621527).

100 Clinical Results associated with ASF1A

100 Translational Medicine associated with ASF1A

0 Patents (Medical) associated with ASF1A

109

Literatures (Medical) associated with ASF1A

01 Jan 2025·Pharmaceutical Research

High Content Image Analysis of Cellular Responses of the Murine J774A.1 Cell Line and Primary Human Cells Alveolar Macrophages to an Extended Panel of Pharmaceutical Agents

Article

Author: Dailey, Lea Ann ; Hädrich, Gabriela ; Schwarzinger, Jacqueline ; Urbano, Laura ; Kollan, Julia ; Tietze, Lysann ; Forbes, Ben ; Eisenmann, Stephan

AbstractIntroductionIn vitro screening of macrophages for drug-induced effects, such as phospholipidosis, is useful for detecting potentially problematic compounds in the preclinical development of oral inhaled products. High-content image analysis (HCIA) is a multi-parameter approach for cytotoxicity screening. This study provides new insights into HCIA-derived response patterns of murine J774A.1 cells and primary human alveolar macrophages (hAM).MethodsSeveral compounds were compared with reference groups (cationic amphiphilic drugs and apoptosis inducers) at different concentrations (0.01 to 10 µM). After incubation, cells were stained with fluorescence markers and HCIA was performed (Cytation™ 5 Cell Imaging System). Ten parameters were analysed: non-adherent cells, increased or reduced mitochondrial activity, membrane permeability, cell area, nuclear area, polynucleated cells, vacuole area, neutral and phospholipid content. A new system of response categorisation was developed for data analysis.ResultsMurine J774A.1 cells exhibited a drug-induced response pattern that was distinct to the corresponding pattern of hAM cells. Comparison with the literature revealed that primary cells (rat or human origin) have similar response patterns, while cell lines (mouse, rat or human) exhibited a different response pattern. Hierarchical clustering revealed toxicologically aligned clusters of compounds, suggesting potential use for understanding mechanisms of drug effects in cell lines and primary cells.ConclusionsValuable information for selecting a suitable cell type for HCIA screening of macrophage responses to drug compounds is provided. All cell types were suitable for screening drug-induced phospholipidosis. Still, human primary alveolar macrophages responded differently to drug treatment compared to macrophage cell lines and may be required to evaluate broader response-patterns and mechanisms of toxicity.

11 Dec 2024·Nucleic Acids Research

CAF-1 promotes efficient PrimPol recruitment to nascent DNA for single-stranded DNA gap formation

Article

Author: Pale, Lindsey ; Moldovan, George-Lucian ; Khatib, Jude B ; Straka, Joshua ; Nicolae, Claudia M

AbstractSuppression of single-stranded DNA (ssDNA) gap accumulation at replication forks has emerged as a potential determinant of chemosensitivity in homologous recombination (HR)-deficient tumors, as ssDNA gaps are transformed into cytotoxic double-stranded DNA breaks. We have previously shown that the histone chaperone CAF-1’s nucleosome deposition function is vital to preventing degradation of stalled replication forks correlating with HR-deficient cells’ response to genotoxic drugs. Here we report that the CAF-1–ASF1 pathway promotes ssDNA gap accumulation at replication forks in both wild-type and breast cancer (BRCA)-deficient backgrounds. We show that this is independent of CAF-1’s nucleosome deposition function but instead may rely on its proper localization to replication forks. Moreover, we show that the efficient localization to nascent DNA of PrimPol, the enzyme responsible for repriming upon replication stress, is dependent on CAF-1. As PrimPol has been shown to be responsible for generating ssDNA gaps as a byproduct of its repriming function, CAF-1’s role in its recruitment could directly impact ssDNA gap formation. We also show that chemoresistance observed in HR-deficient cells when CAF-1 or ASF1A are lost correlates with suppression of ssDNA gaps rather than protection of stalled replication forks. Overall, this work identifies an unexpected role of CAF-1 in regulating PrimPol recruitment and ssDNA gap generation.

01 Oct 2024·Biochemical and Biophysical Research Communications

Structural insights into instability of the nucleosome driven by histone variant H3T

Article

Author: Liu, Yongrui ; Yang, Yang ; Xu, Li ; Hu, Shenglin

The testis-specific histone variant H3T plays a crucial role in chromatin reorganization during spermatogenesis by destabilizing nucleosomes. However, the structure basis for the nucleosome instability driven by H3T is not fully understand. In this study, we determinate the crystal structure of H3T-H4 in complex with histone chaperone ASF1a at 2.8 Å resolution. Our findings reveal that H3T-H4 binds ASF1a similarly to the conventional H3.1-H4 complex. However, significant structural differences are observed in the H3 α1 helix, the N- and C-terminal region of α2, and N-terminal region of L2. These differences are driven by H3T-specific residues, particularly Val111. Unlike the smaller Ala111 in H3.1, we find that bulkier residue Val111 fits well within the ASF1-H3T-H4 complex, but is difficult to arrange in nucleosome structure. Given that H3.1-Ala111/H3T-Val111 is located at the DNA binding and tetramerization interface of H3-H4, it is likely that Ala111Val substitution will lead to the instability of the corresponding area in nucleosome, contributing to instability of H3T-containing nucleosome. These structural findings may elucidate the role of H3T in chromatin reorganization during spermatogenesis.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

ASF1A

Basic Info

Related

Analysis