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The identification of translesion DNA synthesis regulators: Inhibitors in the spotlight

A P Bertolin1, S F Mansilla1, V Gottifredi1

  • 1Cell Cycle Genomic Instability Laboratory, Fundación Instituto Leloir, IIBBA-CONICET, Buenos, Aires, Argentina.

DNA Repair
|May 24, 2015
PubMed

Insights

Translesion DNA synthesis (TLS) repairs damaged DNA but is mutagenic. Researchers are exploring TLS inhibitors, like USP1, p21, and Spartan, to improve chemotherapy by controlling DNA synthesis on damaged templates.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Cells constantly face DNA damage from internal and external sources.
  • Replication of damaged DNA requires specialized translesion DNA synthesis (TLS) polymerases.
  • TLS is inherently mutagenic, necessitating strict regulation to prevent errors on undamaged DNA.

Purpose of the Study:

  • To review methods for validating inhibitors of translesion DNA synthesis (TLS).
  • To highlight research on specific TLS inhibitors: USP1, p21, and Spartan.
  • To discuss the role of these inhibitors in controlling DNA synthesis on damaged and undamaged DNA templates.

Main Methods:

  • Discussion of established methods for validating TLS inhibitors.
  • Review of research studies investigating USP1, p21, and Spartan.
  • Analysis of data concerning DNA synthesis control on damaged templates.

Main Results:

  • Challenges exist in identifying TLS inhibitors due to the lack of direct assays for genomic TLS events.
  • USP1, p21, and Spartan have been investigated as potential TLS inhibitors.
  • Research indicates these inhibitors contribute to regulating DNA synthesis on both damaged and undamaged DNA.

Conclusions:

  • Developing effective TLS inhibitors is crucial for cancer chemotherapy.
  • Further research is needed to refine assays and validate TLS inhibitors.
  • Understanding the precise roles of inhibitors like USP1, p21, and Spartan is key to their clinical application.
Keywords:
DNA replicationMutagenesisPCNASpartanUSP1UV irradiationp21

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