Target intelligence / Profile preview

Chromatin assembly factor 1 subunit A (CHAF1A)

Target
CHAF1A
Molecular classification
Histone chaperone, Chromatin assembly protein, Nuclear protein complex subunit
01

Overview

Chromatin assembly factor 1 subunit A (CHAF1A) is the largest component of the CAF-1 heterotrimeric histone chaperone complex, crucial for assembling newly synthesized histones H3 and H4 onto replicating DNA during the S phase and in DNA repair processes[2][3]. CAF-1 stabilizes and maintains genome structure by mediating the first step of nucleosome assembly at replication forks—acting in concert with proliferating cell nuclear antigen (PCNA)—and helps restore chromatin structure following DNA damage[1][3]. Beyond canonical histone deposition, CHAF1A interacts with the E3 ubiquitin ligase RAD18 to facilitate monoubiquitination of PCNA and regulate the translesion synthesis (TLS) pathway, promoting replication fork restart and elongation under DNA replication stress, especially in cancer cells[1]. Overexpression of CHAF1A correlates with poor prognosis in multiple cancers, and its knockdown results in impaired proliferation and cell cycle arrest, highlighting its essential biological functions and potential as a cancer therapeutic target[1][5].

Other names
Chromatin assembly factor 1 subunit ACHAF1ACAFCAF1P150CAF-1 subunit ACAF-I 150 kDa subunitCAF-I p150hp150CAF1BCAF-1CAF1P150MGC71229Chromatin assembly factor I p150 subunitchromatin assembly factor I (150 kDa)CTB-50L17.7
02

Mechanism of action

no drugs directly targeting CHAF1A; mechanistic roles involve modulation of chromatin assembly and DNA repair, which may be indirectly affected by epigenetic drugs or DNA damage modulators

03

Biological functions

Nucleosome assemblyDNA replicationDNA repair (including translesion synthesis pathway)Heterochromatin maintenanceCell cycle regulation
04

Disease associations

Cancer (e.g., lung cancer, esophageal cancer)Other (e.g., developmental disorders such as craniofacial microsomia)
05

Safety considerations

Potential broad effects on genome stability and cell viability if inhibited, due to essential role in DNA replication and chromatin integrity
06

Biomarkers

Co-overexpression with PCNA as poor prognostic marker in certain cancers (e.g., esophageal cancer)

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