SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi–Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR–CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS–STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.SAMHD1 has an essential role in the replication stress response and prevents inflammation by activating the MRE11 nuclease to degrade nascent DNA strands at stalled replication forks, thus enabling replication.

中文翻译：

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SAMHD1 作用于停滞的复制叉以防止干扰素诱导

SAMHD1 以前被描述为保护细胞免受病毒感染的 dNTPase。SAMHD1 突变与癌症发展和称为 Aicardi-Goutières 综合征的严重先天性炎症有关。SAMHD1 预防癌症和慢性炎症的机制尚不清楚。在这里，我们表明 SAMHD1 通过刺激 MRE11 的核酸外切酶活性，促进人类细胞系中停滞复制叉处新生 DNA 的降解。此函数激活 ATR-CHK1 检查点并允许分叉重新启动复制。在 SAMHD1 耗尽的细胞中，单链 DNA 片段从停滞的叉中释放并在细胞质中积累，在那里它们激活 cGAS-STING 途径以诱导促炎 I 型干扰素的表达。