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DNA Interstrand Crosslink Repair

  1. Wolfram Siede

Published Online: 15 DEC 2009

DOI: 10.1002/9780470015902.a0000575.pub2

eLS

eLS

How to Cite

Siede, W. 2009. DNA Interstrand Crosslink Repair. eLS. .

Author Information

  1. University of North Texas Health Science Center, Fort Worth, Texas, USA

Publication History

  1. Published Online: 15 DEC 2009

This is not the most recent version of the article. View current version (15 AUG 2014)

Abstract

Crosslinking agents such as psoralens, nitrogen mustards or cisplatin are bifunctionally acting chemicals that generate a fraction of their adducts as covalent linkages between complementary deoxyribonucleic acid strands. Since many of these agents are of importance in genetic toxicology and cancer therapy, repair of interstrand crosslinks (ICL) has been studied extensively in prokaryotes and in lower and higher eukaryotes. The main repair pathway in E. coli involves the sequential action of nucleotide excision repair and recombinational repair. In eukaryotes, several repair pathways play important roles not only in repair including nucleotide excision repair, translesion synthesis, recombination, but also mismatch repair. Relative contributions of the various pathways depend on cell cycle position and agent used. Eukaryotic proteins that specifically enhance resistance to crosslinking agents have been identified (SNM1, FANC family of proteins).

Key concepts:

  • Chemicals with two or more correctly spaced reactive groups can covalently link opposing DNA strands.

  • Several repair or tolerance pathways such as nucleotide excision repair, recombination and translesion synthesis can work together to overcome such complex damage.

  • Cell cycle stage may determine the choice of repair pathway combinations.

  • A seemingly deleterious consequence of complex DNA damage (replication fork collapse at a crosslinked site) can be an important integrated part of damage tolerance and repair.

  • A heritable human syndrome with multiple diverse phenotypes (Fanconi anaemia) can be associated with a specific DNA repair deficiency (crosslink repair).

Keywords:

  • DNA repair;
  • crosslinks;
  • excision;
  • alkylation;
  • recombination