Histone chaperone ASF1 acts with RIF1 to promote DNA end joining in BRCA1-deficient cells.
Histone chaperone ASF1 acts with RIF1 to promote DNA end joining in BRCA1-deficient cells.
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DOI：
10.1016/j.jbc.2022.101979
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发表时间：
2022-06
影响因子：
4.8
通讯作者：
Chen, Junjie
中科院分区：
文献类型：
--
作者：
Tang, Mengfan;Chen, Zhen;Wang, Chao;Feng, Xu;Lee, Namsoo;Huang, Min;Zhang, Huimin;Li, Siting;Xiong, Yun;Chen, Junjie
复制定时调节因子1（Replication timing regulatory factor 1，RIF 1）位于p53结合蛋白53 BP 1的下游，抑制DNA断裂末端的切除，在决定DNA双链断裂修复途径选择非同源末端连接还是同源重组（homologous recombination，HR）中起关键作用。然而，作出这种选择的机制尚不清楚。在这项研究中，我们确定了组蛋白伴侣蛋白ASF 1与RIF 1相关，并在DNA损伤反应中调节RIF 1依赖的功能。类似于RIF 1的丢失，我们发现ASF 1的丢失导致BRCA 1缺陷细胞对聚（ADP-核糖）聚合酶（PARP）抑制的抗性，在端粒重复序列结合蛋白2（TRF 2）缺失的细胞中，HR恢复和端粒融合减少。此外，我们发现，这些功能的ASF 1是依赖于它的相互作用与RIF 1，而不是它的组蛋白伴侣活性。因此，我们的研究支持ASF 1在决定双链断裂修复选择中的新作用。考虑到53 BP 1-RIF 1轴的状态在决定BRCA 1或HR缺陷癌症中基于PARP抑制剂的治疗结果方面很重要，在这一关键途径中鉴定ASF 1功能揭示了这些S期事件之间的有趣联系，这可能揭示克服PARP抑制剂耐药性的新策略。
Replication timing regulatory factor 1 (RIF1) acts downstream of p53-binding protein 53BP1 to inhibit the resection of DNA broken ends, which plays critical roles in determining the DNA double-strand break repair pathway choice between nonhomologous end joining and homologous recombination (HR). However, the mechanism by which this choice is made is not yet clear. In this study, we identified that histone chaperone protein ASF1 associates with RIF1 and regulates RIF1-dependent functions in the DNA damage response. Similar to loss of RIF1, we found that loss of ASF1 resulted in resistance to poly (ADP-ribose) polymerase (PARP) inhibition in BRCA1-deficient cells with restored HR and decreased telomere fusion in telomeric repeat–binding protein 2 (TRF2)-depleted cells. Moreover, we showed that these functions of ASF1 are dependent on its interaction with RIF1 but not on its histone chaperone activity. Thus, our study supports a new role for ASF1 in dictating double-strand break repair choice. Considering that the status of 53BP1–RIF1 axis is important in determining the outcome of PARP inhibitor–based therapy in BRCA1- or HR-deficient cancers, the identification of ASF1 function in this critical pathway uncovers an interesting connection between these S-phase events, which may reveal new strategies to overcome PARP inhibitor resistance.
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影响因子：
16.6
作者：
Batenburg NL;Walker JR;Noordermeer SM;Moatti N;Durocher D;Zhu XD
通讯作者：
Zhu XD
影响因子：
4
作者：
Chapman, J. Ross;Sossick, Alex J.;Jackson, Stephen P.
通讯作者：
Jackson, Stephen P.
影响因子：
16
作者：
Davies, AA;Masson, JY;West, SC
通讯作者：
West, SC
由 53BP1-RIF1 和 BRCA1-CtIP 组成的细胞周期依赖性调节回路控制 DNA 修复途径的选择。
影响因子：
16
作者：
Escribano-Diaz, Cristina;Orthwein, Alexandre;Durocher, Daniel
通讯作者：
Durocher, Daniel
DOI：
10.1038/nrm.2016.159
发表时间：
2017-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Hammond CM;Strømme CB;Huang H;Patel DJ;Groth A
通讯作者：
Groth A