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Later work demonstrated that the combined absence of the p53 target genes encoding the pro-apoptotic BH3-only proteins PUMA and NOXA (and to a lesser extent loss of PUMA alone) rendered lymphoid cells as resistant to DNA damage-inducing agents as loss of p53 itself [8, 9, 22]

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This limitation places considerable stress on patients with diseases such as pernicious anemia, which require the use of B12 shots on a regular basis

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