RAD6 promotes homologous recombination repair by activating the autophagy-mediated degradation of heterochromatin protein HP1.
Efficient DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. Unrepaired or misrepaired DSBs cause chromosomal rearrangements that can result in severe consequences, such as tumorigenesis. RAD6 is an E2 ubiquitin-conjugating enzyme that plays a pivotal role in repairing UV-induced DNA damage. Here, we present evidence that RAD6 is also required for DNA DSB repair via homologous recombination (HR) by specifically regulating the degradation of heterochromatin protein 1α (HP1α). Our study indicates that RAD6 physically interacts with HP1α and ubiquitinates HP1α at residue K154, thereby promoting HP1α degradation through the autophagy pathway and eventually leading to an open chromatin structure that facilitates efficient HR DSB repair. Furthermore, bioinformatics studies have indicated that the expression of RAD6 and HP1α exhibits an inverse relationship and correlates with the survival rate of patients.
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Su
S
Chen
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China UNEP-Tongji Institute of Environment for Sustainable Development, Tongji University, Shanghai, People's Republic of China.
Chen
C
Wang
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA School of Medicine, Tsinghua University, Beijing, People's Republic of China.
Luxi
L
Sun
School of Medicine, Tsinghua University, Beijing, People's Republic of China.
Da-Liang
DL
Wang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Lu
L
Chen
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Zhuan
Z
Huang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Qi
Q
Yang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Jie
J
Gao
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Xi-Bin
XB
Yang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Jian-Feng
JF
Chang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Ping
P
Chen
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Li
L
Lan
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China zhiyong_mao@tongji.edu.cn sfl@tongji.edu.cn.
Zhiyong
Z
Mao
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China zhiyong_mao@tongji.edu.cn sfl@tongji.edu.cn.
Fang-Lin
FL
Sun
D001343:Autophagy / Q000235:genetics*; D002460:Cell Line; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism*; D006801:Humans; D059767:Recombinational DNA Repair / Q000235:genetics*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D000090266:Chromobox Protein Homolog 5; C471545:UBE2A protein, human; C471546:UBE2B protein, human; D044763:Ubiquitin-Conjugating Enzymes