Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI

Sun，Siyuan1; He，Hengqian1; Ma，Yuanyuan2; Xu，Jie3; Chen，Guoan4; Sun，Yi1; Xiong，Xiufang1

2020-10-01

10.1038/s41419-020-03082-9

Cell Death & Disease   影响因子和分区

2041-4889

2041-4889

Ribosomal protein S27-like (RPS27L), an evolutionarily conserved ribosomal protein and a direct p53 target, plays an important role in maintenance of genome integrity. We have previously reported that RPS27L regulates radiation sensitivity via the MDM2-p53 and MDM2-MRN-ATM axes. Whether and how RPS27L modulates DNA interstrand cross-link (ICL) repair is unknown. Here we identified that RPS27L binds to FANCD2 and FANCI, two Fanconi anemia (FA) proteins functioning in ICL repair pathway. Upon RPS27L knockdown, the levels of FANCD2 and FANCI are reduced due to accelerated degradation via p62-mediated autophagy-lysosome pathway, which is abrogated by chloroquine (CQ) treatment or Beclin 1 knockdown. Biologically, RPS27L knockdown suppresses FANCD2 foci formation and impairs ICL repair upon exposure to ICL-inducing agent mitomycin C (MMC) in lung cancer cells. This effect of MMC sensitization can be partially reversed by CQ treatment. Together, our study shows that RPS27L positively regulates ICL repair by binding with FANCD2 and FANCI to prevent their degradation via autophagy-lysosome system.

SCI

英语

其他

National Natural Science Foundation of China[81572708][81974429][31501129][31600655][81572718][81630076] ; National Key R&D Program of China[2016YFA0501800]

Cell Biology

Cell Biology

WOS:000581611200006

SPRINGERNATURE

2-s2.0-85092521950

Scopus

1.Cancer Institute of the Second Affiliated Hospital,and Institute of Translational Medicine,Zhejiang University School of Medicine,Hangzhou,China
2.Shanghai Institute of Precision Medicine,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China
3.Department of Urology,the Second Affiliated Hospital,Third Military Medical University (Army Medical University),Chongqing,China
4.School of Medicine,Southern University of Science and Technology,Shenzhen,China

Sun，Siyuan,He，Hengqian,Ma，Yuanyuan,et al. Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI[J]. Cell Death & Disease,2020,11(10).

Sun，Siyuan.,He，Hengqian.,Ma，Yuanyuan.,Xu，Jie.,Chen，Guoan.,...&Xiong，Xiufang.(2020).Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI.Cell Death & Disease,11(10).

Sun，Siyuan,et al."Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI".Cell Death & Disease 11.10(2020).