HP1 regulates the localization of FANCJ at sites of DNA double-strand breaks.
HP1 regulates the localization of FANCJ at sites of DNA double-strand breaks.
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HP1调节FANCJ在DNA双链断裂部位的定位。
DOI：
10.1111/cas.13008
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发表时间：
2016-10
期刊：
影响因子：
5.7
通讯作者：
Ohta T
中科院分区：
文献类型：
--
作者：
Wu W;Togashi Y;Johmura Y;Miyoshi Y;Nobuoka S;Nakanishi M;Ohta T
乳腺癌和卵巢癌易感蛋白BRCA 1通过其BRCA 1 C末端（BRCT）结构域与范可尼贫血J组蛋白（FANCJ，也称为BACH 1或BRIP 1），CtIP和Abraxas/RAP 80形成三种相互排斥的复合物，而其RING结构域与BRCA 1相关的RING结构域1（BARD 1）结合。我们最近发现，异染色质蛋白1（HP 1）和BARD 1之间的相互作用是BRCA 1和CtIP在DNA双链断裂位点积累所必需的。在这里，我们研究了HP 1和BARD 1-HP 1相互作用在FANCJ与其他BRCA 1-BRCT结合蛋白定位中的重要性，以阐明HP 1介导的通路与RNF 8/RNF 168诱导的泛素介导的通路对BRCA 1功能的不同作用。FANCJ以BARD 1依赖性方式与HP 1 γ相互作用，电离辐射或盐酸伊立替康处理可增强这种相互作用。用shRNA同时消耗所有三种HP 1亚型会破坏FANCJ和CtIP在双链断裂位点的积累，但不会破坏RAP 80。用不能与HP 1结合的突变体BARD 1替换内源性BARD 1也破坏FANCJ和CtIP的积累，但不破坏RAP 80。相比之下，RNF 168耗尽仅破坏RAP 80的积累，而不是FANCJ或CtIP。因此，结合的泛素的积累仅受RNF 168耗竭的抑制，而RAD 51的积累和姐妹染色单体交换仅受HP 1耗竭或BARD 1-HP 1相互作用的破坏的抑制。总之，结果表明BRCA 1-FANCJ和BRCA 1-CtIP复合物不是RNF 8/RNF 168/泛素途径的下游，而是由同源重组DNA修复之前的HP 1途径调节。
The breast and ovarian cancer predisposition protein BRCA1 forms three mutually exclusive complexes with Fanconi anemia group J protein (FANCJ, also called BACH1 or BRIP1), CtIP, and Abraxas/RAP80 through its BRCA1 C terminus (BRCT) domains, while its RING domain binds to BRCA1‐associated RING domain 1 (BARD1). We recently found that the interaction between heterochromatin protein 1 (HP1) and BARD1 is required for the accumulation of BRCA1 and CtIP at sites of DNA double‐strand breaks. Here, we investigated the importance of HP1 and BARD1–HP1 interaction in the localization of FANCJ together with the other BRCA1–BRCT binding proteins to clarify the separate role of the HP1‐mediated pathway from the RNF8/RNF168‐induced ubiquitin‐mediated pathway for BRCA1 function. FANCJ interacts with HP1γ in a BARD1‐dependent manner, and this interaction was enhanced by ionizing radiation or irinotecan hydrochloride treatment. Simultaneous depletion of all three HP1 isoforms with shRNAs disrupts the accumulation of FANCJ and CtIP, but not RAP80, at double‐strand break sites. Replacement of endogenous BARD1 with a mutant BARD1 that is incapable of binding to HP1 also disrupts the accumulation of FANCJ and CtIP, but not RAP80. In contrast, RNF168 depletion disrupts the accumulation of only RAP80, but not FANCJ or CtIP. Consequently, the accumulation of conjugated ubiquitin was only inhibited by RNF168 depletion, whereas the accumulation of RAD51 and sister chromatid exchange were only inhibited by HP1 depletion or disruption of the BARD1–HP1 interaction. Taken together, the results suggest that the BRCA1–FANCJ and BRCA1–CtIP complexes are not downstream of the RNF8/RNF168/ubiquitin pathway, but are instead regulated by the HP1 pathway that precedes homologous recombination DNA repair.
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DOI：
10.1083/jcb.200510130
发表时间：
2006-04-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bekker-Jensen S;Lukas C;Kitagawa R;Melander F;Kastan MB;Bartek J;Lukas J
通讯作者：
Lukas J
影响因子：
8.8
作者：
Khurana S;Kruhlak MJ;Kim J;Tran AD;Liu J;Nyswaner K;Shi L;Jailwala P;Sung MH;Hakim O;Oberdoerffer P
通讯作者：
Oberdoerffer P
影响因子：
3.7
作者：
Brosh RM Jr;Cantor SB
通讯作者：
Cantor SB
影响因子：
4.8
作者：
Hashizume, R;Fukuda, M;Ohta, T
通讯作者：
Ohta, T
影响因子：
8.8
作者：
Cruz-Garcia, Andres;Lopez-Saavedra, Ana;Huertas, Pablo
通讯作者：
Huertas, Pablo