🖐 イルファーン・カーン - Wikipedia

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We delineated the molecular defects of two FA patient-derived FANCJ helicase domain mutations.

Of over 20 FA-linked genes, Irfan khan uniquely encodes a DNA helicase and mutations are also associated with breast and ovarian cancer. Live-cell imaging demonstrated a significantly compromised recruitment of FANCJ-RC to irfan khan DNA damage. Expression of FANCJ-RC or FANCJ-HD in fancj -cells failed to rescue cisplatin or irfan khan sensitivity.

FANCJ-RC was compromised in dimerization and helicase processivity, whereas DNA unwinding by FANCJ-HD was barely detectable. AB - Fanconi Anemia FA is characterized by bone marrow failure, congenital abnormalities, and cancer.

Thus, a minimal threshold of FANCJ catalytic activity is required to overcome replication stress induced by aphidicolin or telomestatin, or to repair bleomycin-induced DNA breakage. These findings have implications for therapeutic strategies relying on DNA cross-link sensitivity or heightened replication stress characteristic of cancer cells. DNA binding and ATP hydrolysis was defective for both FANCJ-RC and FANCJ-HD, the latter showing greater reduction. fancj -cells are sensitive to DNA interstrand cross-linking ICL and replication fork stalling drugs.