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Repair of genomic interstrand crosslinks.

Marina A Bellani1, Althaf Shaik1, Ishani Majumdar1

  • 1Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

DNA Repair
|August 6, 2024
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Summary

Genomic interstrand crosslinks (ICLs) are repaired by unhooking DNA strands. This review details ICL compounds, repair mechanisms, and their role in cancer drug resistance and metabolism.

Keywords:
Cancer chemotherapyDNA repairDrug resistanceInterstrand crosslinkUnhooking

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Genomic interstrand crosslinks (ICLs) arise from metabolism, microbiome activity, and chemotherapy.
  • ICL repair is essential, with strand unhooking being a critical step.
  • Model systems using plasmids have been key to understanding ICL unhooking mechanisms.

Purpose of the Study:

  • To review properties of ICL-forming compounds, both exogenous and endogenous.
  • To provide historical context for early ICL repair research.
  • To discuss ICL unhooking mechanisms and their relevance in drug-resistant tumors and metabolic aldehydes.

Main Methods:

  • Review of existing literature on ICL-forming compounds and repair pathways.
  • Analysis of data from model systems (plasmids in cells/cell-free extracts).
  • Discussion of clinical relevance in drug-resistant tumors.

Main Results:

  • ICLs are formed through various endogenous and exogenous sources.
  • Multiple ICL repair pathways exist, all involving DNA strand unhooking.
  • Model systems reveal diverse unhooking mechanisms, with varying concordance in tumors.

Conclusions:

  • Understanding ICL formation and repair is crucial for cancer therapy and cellular metabolism.
  • The study of ICLs in model systems provides fundamental insights into DNA repair.
  • Further research is needed to fully elucidate ICL roles in drug resistance and metabolic processes.