Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

Min Gao; Wei Wei; Ming Hua Li; Yong-Sheng Wu; Zhaoqing Ba; Kang-Xuan Jin; Miao-Miao Li; You-Qi Liao; Samir Adhikari; Zechen Chong; Ting Zhang; Cai-Xia Guo; Tie-Shan Tang; Bing-Tao Zhu; Xing-Zhi Xu; Niels Mailand; Yun-Gui Yang; Yijun Qi; Jannie Michaela Rendtlew Danielsen

doi:10.1038/cr.2014.36

Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

Min Gao, Wei Wei, Ming Hua Li, Yong-Sheng Wu, Zhaoqing Ba, Kang-Xuan Jin, Miao-Miao Li, You-Qi Liao, Samir Adhikari, Zechen Chong, Ting Zhang, Cai-Xia Guo, Tie-Shan Tang, Bing-Tao Zhu, Xing-Zhi Xu, Niels Mailand, Yun-Gui Yang, Yijun Qi, Jannie Michaela Rendtlew Danielsen

The NNF Center for Protein Research

112 Citationer (Scopus)

Abstract

DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with Rad51 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that Rad51 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs to facilitate repair by HR.

Originalsprog	Engelsk
Tidsskrift	Cell Research
Vol/bind	24
Udgave nummer	5
Sider (fra-til)	532-41
Antal sider	10
ISSN	1001-0602
DOI	https://doi.org/10.1038/cr.2014.36
Status	Udgivet - maj 2014

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10.1038/cr.2014.36

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Gao, M., Wei, W., Li, M. H., Wu, Y.-S., Ba, Z., Jin, K.-X., Li, M.-M., Liao, Y.-Q., Adhikari, S., Chong, Z., Zhang, T., Guo, C.-X., Tang, T.-S., Zhu, B.-T., Xu, X.-Z., Mailand, N., Yang, Y.-G., Qi, Y., & Danielsen, J. M. R. (2014). Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination. Cell Research, 24(5), 532-41. https://doi.org/10.1038/cr.2014.36

Gao, M, Wei, W, Li, MH, Wu, Y-S, Ba, Z, Jin, K-X, Li, M-M, Liao, Y-Q, Adhikari, S, Chong, Z, Zhang, T, Guo, C-X, Tang, T-S, Zhu, B-T, Xu, X-Z, Mailand, N, Yang, Y-G, Qi, Y & Danielsen, JMR 2014, 'Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination', Cell Research, bind 24, nr. 5, s. 532-41. https://doi.org/10.1038/cr.2014.36

@article{4d00bc3ac0c244e89772435aa9102a6f,

title = "Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination",

abstract = "DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with Rad51 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that Rad51 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs to facilitate repair by HR.",

author = "Min Gao and Wei Wei and Li, {Ming Hua} and Yong-Sheng Wu and Zhaoqing Ba and Kang-Xuan Jin and Miao-Miao Li and You-Qi Liao and Samir Adhikari and Zechen Chong and Ting Zhang and Cai-Xia Guo and Tie-Shan Tang and Bing-Tao Zhu and Xing-Zhi Xu and Niels Mailand and Yun-Gui Yang and Yijun Qi and Danielsen, {Jannie Michaela Rendtlew}",

year = "2014",

month = may,

doi = "10.1038/cr.2014.36",

language = "English",

volume = "24",

pages = "532--41",

journal = "Cell Research",

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TY - JOUR

T1 - Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

AU - Gao, Min

AU - Wei, Wei

AU - Li, Ming Hua

AU - Wu, Yong-Sheng

AU - Ba, Zhaoqing

AU - Jin, Kang-Xuan

AU - Li, Miao-Miao

AU - Liao, You-Qi

AU - Adhikari, Samir

AU - Chong, Zechen

AU - Zhang, Ting

AU - Guo, Cai-Xia

AU - Tang, Tie-Shan

AU - Zhu, Bing-Tao

AU - Xu, Xing-Zhi

AU - Mailand, Niels

AU - Yang, Yun-Gui

AU - Qi, Yijun

AU - Danielsen, Jannie Michaela Rendtlew

PY - 2014/5

Y1 - 2014/5

N2 - DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with Rad51 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that Rad51 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs to facilitate repair by HR.

AB - DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with Rad51 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that Rad51 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs to facilitate repair by HR.

U2 - 10.1038/cr.2014.36

DO - 10.1038/cr.2014.36

M3 - Journal article

C2 - 24662483

SN - 1001-0602

VL - 24

SP - 532

EP - 541

JO - Cell Research

JF - Cell Research

IS - 5

ER -

Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

Abstract

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