Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress
Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress
复制标题
范可尼贫血蛋白参与断裂诱导复制样途径来对抗复制应激
DOI：
10.1038/s41594-021-00602-9
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Dongyi Xu
中科院分区：
文献类型：
--
作者：
Xinlin Xu;Yixi Xu;Ruiyuan Guo;Ran Xu;Congcong Fu;Mengtan Xing;Hiroyuki Sasanuma;Qing Li;Minoru Takata;Shunichi Takeda;Rong Guo;Dongyi Xu
范可尼贫血（FA）是一种以骨髓衰竭（BMF）和急性髓系白血病（AML）为特征的毁灭性遗传性疾病。由于FA缺陷细胞对DNA链间交联（ICL）高度敏感，因此ICL被广泛认为是FA症状的病变。在这里，我们发现FA突变的细胞对持续的复制应激是高度敏感的，并且FA蛋白在中断诱导复制（BIR）样途径中起作用。BIR-like途径和ICL修复具有几乎相同的分子机制，即53 BP 1-BRCA 1控制的信号应答、SLX 4和FAN 1介导的叉切割和POLD 3依赖的DNA合成，这表明FA途径本质上是BIR-like途径之一。复制应激不仅在FA缺陷小鼠中触发BMF，而且在FA缺陷细胞中特异性诱导单体7，其与FA患者向AML的进展相关。
Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1–BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells.
登录
查看更多内容
影响因子：
16
作者：
Long, David T.;Joukov, Vladimir;Budzowska, Magda;Walter, Johannes C.
通讯作者：
Walter, Johannes C.
影响因子：
16.6
作者：
Ahuja AK;Jodkowska K;Teloni F;Bizard AH;Zellweger R;Herrador R;Ortega S;Hickson ID;Altmeyer M;Mendez J;Lopes M
通讯作者：
Lopes M
DOI：
10.1074/jbc.m117.814780
发表时间：
2017-10
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Yanyan Tian;Xi Shen;Rui Wang;Naeh L. Klages-Mundt;E. Lynn;Sara K. Martin;Yin Ye;Min Gao;Junjie Chen;K. Schlacher;Lei Li
通讯作者：
Yanyan Tian;Xi Shen;Rui Wang;Naeh L. Klages-Mundt;E. Lynn;Sara K. Martin;Yin Ye;Min Gao;Junjie Chen;K. Schlacher;Lei Li
复制应激激活有丝分裂中的 DNA 修复合成
影响因子：
64.8
作者：
Minocherhomji, Sheroy;Ying, Songmin;Hickson, Ian D.
通讯作者：
Hickson, Ian D.
影响因子：
16
作者：
Shen X;Wang R;Kim MJ;Hu Q;Hsu CC;Yao J;Klages-Mundt N;Tian Y;Lynn E;Brewer TF;Zhang Y;Arun B;Gan B;Andreeff M;Takeda S;Chen J;Park JI;Shi X;Chang CJ;Jung SY;Qin J;Li L
通讯作者：
Li L