Sp1-independent downregulation of NHEJ in response to BER deficiency

Polina S. Loshchenova, Svetlana V. Sergeeva, Dmitry V. Limonov, Zhigang Guo, Grigory L. Dianov

Research output: Contribution to journalArticlepeer-review


Base excision repair (BER) is the major repair pathway that removes DNA single strand breaks (SSBs) arising spontaneously due to the inherent instability of DNA. Unrepaired SSBs promote cell-cycle delay, which facilitates DNA repair prior to replication. On the other hand, in response to persistent DNA strand breaks, ATM-dependent degradation of transcription factor Sp1 leads to downregulation of BER genes expression, further accumulation of SSBs and renders cells susceptible to elimination via apoptosis. In contrast, many cancer cells are not able to block replication and to downregulate the expression of Sp1 in response to DNA damage. However, knockdown of BER in cancer cells leads to the accumulation of DNA double strand breaks (DSBs), suggesting deficiency in non-homologous end joining (NHEJ) repair of DSBs. Here we investigated whether DNA repair deficiency caused by knockdown of the XRCC1 gene expression in proliferating cells results in downregulation of NHEJ genes expression. We find that knockdown of the XRCC1 gene expression does not cause degradation of Sp1, but leads to downregulation of Lig4/XRCC4 and Ku70/80 at the transcription and protein levels. We thus propose the existence of Sp1-independent backup mechanism that in response to BER deficiency downregulates NHEJ in proliferating cells.

Original languageEnglish
Article number102740
Number of pages6
JournalDNA Repair
Publication statusPublished - 1 Feb 2020


  • Base excision repair (BER)
  • DNA damage
  • Genome stability
  • Non-homologous End joining (NHEJ)
  • Transcription factor Sp1
  • Cell Line
  • Cell Proliferation
  • Signal Transduction
  • Sp1 Transcription Factor/metabolism
  • Down-Regulation
  • Humans
  • X-ray Repair Cross Complementing Protein 1/genetics
  • DNA Breaks, Double-Stranded
  • Gene Knockdown Techniques
  • DNA End-Joining Repair
  • DNA Repair


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