Distinctive roles of translesion polymerases DinB1 and DnaE2 in diversification of the mycobacterial genome through substitution and frameshift mutagenesis Journal Article

   


Authors: Dupuy, P.; Ghosh, S.; Adefisayo, O.; Buglino, J.; Shuman, S.; Glickman, M. S.
Article Title: Distinctive roles of translesion polymerases DinB1 and DnaE2 in diversification of the mycobacterial genome through substitution and frameshift mutagenesis
Abstract: Antibiotic resistance of Mycobacterium tuberculosis is exclusively a consequence of chromosomal mutations. Translesion synthesis (TLS) is a widely conserved mechanism of DNA damage tolerance and mutagenesis, executed by translesion polymerases such as DinBs. In mycobacteria, DnaE2 is the only known agent of TLS and the role of DinB polymerases is unknown. Here we demonstrate that, when overexpressed, DinB1 promotes missense mutations conferring resistance to rifampicin, with a mutational signature distinct from that of DnaE2, and abets insertion and deletion frameshift mutagenesis in homo-oligonucleotide runs. DinB1 is the primary mediator of spontaneous −1 frameshift mutations in homo-oligonucleotide runs whereas DnaE2 and DinBs are redundant in DNA damage-induced −1 frameshift mutagenesis. These results highlight DinB1 and DnaE2 as drivers of mycobacterial genome diversification with relevance to antimicrobial resistance and host adaptation. © 2022, The Author(s).
Keywords: frameshift mutation; genetics; missense mutation; mutation; mutation, missense; dna replication; dna damage; gene; dna repair; enzyme activity; bacterial protein; mycobacterium tuberculosis; bacterial proteins; dna; genome; oligonucleotide; mutagenesis; bacterium; tuberculosis; oligonucleotides; enzyme; nucleotidyltransferase; nucleotidyltransferases; mutagenicity
Journal Title: Nature Communications
Volume: 13
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2022-08-02
Start Page: 4493
Language: English
DOI: 10.1038/s41467-022-32022-8
PUBMED: 35918328
PROVIDER: scopus
PMCID: PMC9346131
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135242225&doi=10.1038%2fs41467-022-32022-8&partnerID=40&md5=f7b8c305f0d35d1d20b0cbc6b3981e59
Notes: Article -- Export Date: 1 September 2022 -- Source: Scopus
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MSK Authors
  1. Stewart H Shuman
    546 Shuman
  2. John A Buglino
    10 Buglino
  3. Michael Glickman
    109 Glickman
  4. Shreya Ghosh
    12 Ghosh
  5. Pierre Dupuy
    5 Dupuy
  6. Oyindamola O Adefisayo
    3 Adefisayo
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