Fanconi anemia associated protein 20 (FAAP20) plays an essential role in homology-directed repair of DNA double-strand breaks.
Fanconi anemia associated protein 20 (FAAP20) plays an essential role in homology-directed repair of DNA double-strand breaks.
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DOI：
10.1038/s42003-023-05252-9
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发表时间：
2023-08-24
影响因子：
5.9
通讯作者：
Zhang, Yanbin
中科院分区：
文献类型：
--
作者：
Palovcak, Anna;Yuan, Fenghua;Verdun, Ramiro;Luo, Liang;Zhang, Yanbin
FAAP20是一种Fanconi贫血(FA)蛋白，它与FANCD2/FANCI核心复合体结合，促进FANCD2/FANCI单素化，激活对链间交联损伤的损伤反应。在这里，我们报告了FAAP20在DNA双链断裂的同源重组中起着显著的作用，该双链断裂与ICL无关，可与其结合伙伴FANCA分离。虽然FAAP20的S在同源重组中的作用不依赖于FANCA，但我们发现FAAP20在体外刺激FANCA的生化活性，并以FANCA依赖的方式参与双链断裂修复的单链退火途径。这表明FAAP20在几个同源定向的修复途径中具有作用。像其他同源导向的修复因子一样，FAAP20的缺失导致核RAD51辐射诱导的焦点减少；并使癌细胞对电离辐射和PARP抑制敏感。综上所述，FAAP20通过非冗余方式支持与FANCA的同源重组参与DNA双链断裂修复，并通过FANCA介导的链退火活性支持单链退火修复。FAAP20在DNA双链断裂修复的几个同源定向途径中发挥作用，这些途径既独立又依赖于其结合伙伴FANCA和FANCA介导的单链退火。
FAAP20 is a Fanconi anemia (FA) protein that associates with the FA core complex to promote FANCD2/FANCI monoubiquitination and activate the damage response to interstrand crosslink damage. Here, we report that FAAP20 has a marked role in homologous recombination at a DNA double-strand break not associated with an ICL and separable from its binding partner FANCA. While FAAP20’s role in homologous recombination is not dependent on FANCA, we found that FAAP20 stimulates FANCA’s biochemical activity in vitro and participates in the single-strand annealing pathway of double-strand break repair in a FANCA-dependent manner. This indicates that FAAP20 has roles in several homology-directed repair pathways. Like other homology-directed repair factors, FAAP20 loss causes a reduction in nuclear RAD51 Irradiation-induced foci; and sensitizes cancer cells to ionizing radiation and PARP inhibition. In summary, FAAP20 participates in DNA double strand break repair by supporting homologous recombination in a non-redundant manner to FANCA, and single-strand annealing repair via FANCA-mediated strand annealing activity. FAAP20 has roles in several homology-directed pathways of DNA double-strand break repair that are both independent and dependent on its binding partner FANCA and FANCA-mediated single strand annealing.
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