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Review
. 2010 Jul;51(6):540-51.
doi: 10.1002/em.20566.

Repair of DNA interstrand cross-links during S phase of the mammalian cell cycle

Randy J Legerski  1
Affiliations
Review

Repair of DNA interstrand cross-links during S phase of the mammalian cell cycle

Randy J Legerski. Environ Mol Mutagen. 2010 Jul.

Abstract

DNA interstrand cross-linking (ICL) agents are widely used in anticancer chemotherapy regimens, yet our understanding of the DNA repair mechanisms by which these lesions are removed from the genome remains incomplete. This is at least in part due to the enormously complicated nature and variety of the biochemical pathways that operate on these complex lesions. In this review, we have focused specifically on the S-phase pathway of ICL repair in mammalian cells, which appears to be the major mechanism by which these lesions are removed in cycling cells. The various stages and components of this pathway are discussed, and a putative molecular model is presented. In addition, we propose an explanation as to how this pathway can lead to the observed high levels of sister chromatid exchanges known to be induced by ICLs.

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Figures

Figure 1
Figure 1
Putative model for the repair of ICLs during S phase in mammalian cells. “Ub” indicates ubiquitin. See text for details.
Figure 2
Figure 2
BIR leads to SCE. Schematic illustrating a mechanism by which recombination-mediated fork restart results in SCE in a pathway that is independent of BLM. The parental strand shown in red indicates labeling occurring during the previous S phase of the cell cycle. See text for details.
See this image and copyright information in PMC

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