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R‐loops mediate transcription‐associated formation of human rDNA secondary constrictions
Author(s) -
Zhou Hong,
Wang Yapei,
Wang Qing,
Li Le,
Hu Yan,
Wu Yequn,
Gautam Mayank,
Li Lijia
Publication year - 2021
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.30074
Subject(s) - biology , transcription (linguistics) , secondary constriction , ribosomal dna , dna , microbiology and biotechnology , topoisomerase , genetics , gene , chromosome , centromere , philosophy , linguistics , phylogenetics
Abstract The ribosomal gene DNA (rDNA) often forms secondary constrictions in the chromosome; however, the molecular mechanism involved remains poorly understood. Here, we report that occurrence of rDNA constriction was increased in the chromosomes in human cancer cell lines compared with normal cells and that decondensed rDNA was significantly enhanced after partial inhibition of rDNA transcription. rDNA transcription was found during the S phase when replication occurred, and thus, DNA replication inhibitors caused constriction formation through hindering rDNA transcription. Inhibition of ataxia ATR (telangiectasia‐mutated and RAD3‐related) induced rDNA constriction formation. Replication stress or transcription inhibition increased R‐loop formation. Topoisomerase I and RNase H1 suppressed secondary constriction formation. These data demonstrate that transcription stress causes the accumulation of stable R‐loops (RNA–DNA hybrid) and subsequent constriction formation in the chromosomes.