FANCJ DNA helicase is recruited to the replisome by AND-1 to ensure genome stability.

Autor:	Boavida A; Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Naples, Italy.; Università degli Studi della Campania 'Luigi Vanvitelli', Caserta, Italy., Napolitano LM; Structural Biology Laboratory, Elettra-Sincrotrone Trieste, Trieste, Italy., Santos D; Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Naples, Italy.; Università degli Studi della Campania 'Luigi Vanvitelli', Caserta, Italy., Cortone G; Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Naples, Italy., Jegadesan NK; IFOM ETS-The AIRC Institute of Molecular Oncology, Milan, Italy., Onesti S; Structural Biology Laboratory, Elettra-Sincrotrone Trieste, Trieste, Italy., Branzei D; IFOM ETS-The AIRC Institute of Molecular Oncology, Milan, Italy.; Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy., Pisani FM; Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Naples, Italy. francesca.pisani@ibbc.cnr.it.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Feb; Vol. 25 (2), pp. 876-901. Date of Electronic Publication: 2024 Jan 02.
DOI:	10.1038/s44319-023-00044-y
Abstrakt:	FANCJ, a DNA helicase linked to Fanconi anemia and frequently mutated in cancers, counteracts replication stress by dismantling unconventional DNA secondary structures (such as G-quadruplexes) that occur at the DNA replication fork in certain sequence contexts. However, how FANCJ is recruited to the replisome is unknown. Here, we report that FANCJ directly binds to AND-1 (the vertebrate ortholog of budding yeast Ctf4), a homo-trimeric protein adaptor that connects the CDC45/MCM2-7/GINS replicative DNA helicase with DNA polymerase α and several other factors at DNA replication forks. The interaction between FANCJ and AND-1 requires the integrity of an evolutionarily conserved Ctf4-interacting protein (CIP) box located between the FANCJ helicase motifs IV and V. Disruption of the CIP box significantly reduces FANCJ association with the replisome, causing enhanced DNA damage, decreased replication fork recovery and fork asymmetry in cells unchallenged or treated with Pyridostatin, a G-quadruplex-binder, or Mitomycin C, a DNA inter-strand cross-linking agent. Cancer-relevant FANCJ CIP box variants display reduced AND-1-binding and enhanced DNA damage, a finding that suggests their potential role in cancer predisposition. (© 2024. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu