Rad9/53BP1 保护停滞的复制叉免受 Mek1/ATR 缺陷细胞的降解。
Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR-defective cells.
机构信息
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy
出版信息
EMBO Rep. 2018 Feb;19(2):351-367. doi: 10.15252/embr.201744910. Epub 2018 Jan 4.
Abstract
Nucleolytic processing by nucleases can be a relevant mechanism to allow repair/restart of stalled replication forks. However, nuclease action needs to be controlled to prevent overprocessing of damaged replication forks that can be detrimental to genome stability. The checkpoint protein Rad9/53BP1 is known to limit nucleolytic degradation (resection) of DNA double-strand breaks (DSBs) in both yeast and mammals. Here, we show that loss of the inhibition that Rad9 exerts on resection exacerbates the sensitivity to replication stress of Mec1/ATR-defective yeast cells by exposing stalled replication forks to Dna2-dependent degradation. This Rad9 protective function is independent of checkpoint activation and relies mainly on Rad9-Dpb11 interaction. We propose that Rad9/53BP1 supports cell viability by protecting stalled replication forks from extensive resection when the intra-S checkpoint is not fully functional.
摘要
核酸酶的核酸内切作用可能是一种相关的机制，允许修复/重新启动停滞的复制叉。然而，需要控制核酸酶的作用，以防止过度处理受损的复制叉，这可能对基因组稳定性有害。已知检查点蛋白 Rad9/53BP1 可限制酵母和哺乳动物中 DNA 双链断裂 (DSB) 的核酸内切降解 (切除)。在这里，我们表明，Rad9 对切除的抑制作用的丧失通过使停滞的复制叉暴露于 Dna2 依赖性降解，加剧了 mec1/atr 缺陷酵母细胞对复制应激的敏感性。这种 Rad9 的保护功能不依赖于检查点的激活，主要依赖于 Rad9-Dpb11 相互作用。我们提出，当内 S 检查点不完全功能时，Rad9/53BP1 通过保护停滞的复制叉免受广泛的切除，从而支持细胞存活。
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