Rtt105 functions as a chaperone for replication protein A to preserve genome stability

Shuqi Li, Zhiyun Xu, Jiawei Xu, Linyu Zuo, Chuanhe Yu, Pu Zheng, Haiyun Gan, Xuezheng Wang, Longtu Li, Sushma Sharma, Andrei Chabes, Di Li, Sheng Wang, Sihao Zheng, Jinbao Li, Xuefeng Chen, Yujie Sun, Dongyi Xu, Junhong Han, Kuiming ChanZhi Qi, Jianxun Feng, Qing Li

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Generation of single-stranded DNA (ssDNA) is required for the template strand formation during DNA replication. Replication Protein A (RPA) is an ssDNA-binding protein essential for protecting ssDNA at replication forks in eukaryotic cells. While significant progress has been made in characterizing the role of the RPA–ssDNA complex, how RPA is loaded at replication forks remains poorly explored. Here, we show that the Saccharomyces cerevisiae protein regulator of Ty1 transposition 105 (Rtt105) binds RPA and helps load it at replication forks. Cells lacking Rtt105 exhibit a dramatic reduction in RPA loading at replication forks, compromised DNA synthesis under replication stress, and increased genome instability. Mechanistically, we show that Rtt105 mediates the RPA–importin interaction and also promotes RPA binding to ssDNA directly in vitro, but is not present in the final RPA–ssDNA complex. Single-molecule studies reveal that Rtt105 affects the binding mode of RPA to ssDNA. These results support a model in which Rtt105 functions as an RPA chaperone that escorts RPA to the nucleus and facilitates its loading onto ssDNA at replication forks.

Original languageEnglish (US)
Article numbere99154
JournalEMBO Journal
Volume37
Issue number17
DOIs
StatePublished - Sep 3 2018
Externally publishedYes

Keywords

  • RPA chaperone
  • Rtt105
  • replication fork
  • replication stress

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    Li, S., Xu, Z., Xu, J., Zuo, L., Yu, C., Zheng, P., Gan, H., Wang, X., Li, L., Sharma, S., Chabes, A., Li, D., Wang, S., Zheng, S., Li, J., Chen, X., Sun, Y., Xu, D., Han, J., ... Li, Q. (2018). Rtt105 functions as a chaperone for replication protein A to preserve genome stability. EMBO Journal, 37(17), [e99154]. https://doi.org/10.15252/embj.201899154