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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].
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
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