Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jun;2(3):144-154.
doi: 10.3978/j.issn.2218-676X.2013.03.01.

DNA crosslinking damage and cancer - a tale of friend and foe

Yaling Huang  1 , Lei Li
Affiliations

DNA crosslinking damage and cancer - a tale of friend and foe

Yaling Huang et al. Transl Cancer Res. 2013 Jun.

Abstract

Interstrand crosslinks (ICLs) represent a major challenge for DNA replication and transcription by preventing DNA strand separation. Cells deficient in ICL repair are hypersensitive to a variety of bifunctional alkylating agents and exhibit excessive genomic instability. Patients with deficient ICL repair, such as those with Fanconi anemia, are predisposed to a broad spectrum of cancers. The profound cellular toxicity of ICLs is exploited clinically in cancer chemotherapy. Therefore, understanding the mechanism of ICL repair and its impact on cancer development and treatment is very important. Studies of diseases with defective ICL repair, especially Fanconi anemia, have revealed unique ICL repair mechanisms in humans. In this review, we describe pathways and factors involved in ICL damage response and their implications in cancer development and treatment.

Keywords: DNA repair; Fanconi anemia; Interstrand crosslink; cancer.

PubMed Disclaimer

Conflict of interest statement

Disclosure: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Interstrand crosslink repair pathway in prokaryotes. This pathway includes nucleotide excision repair and homologous recombination, which is error free (indicated as blue DNA patches). Note, this model is adapted from the one proposed by Cole. et al. in 1973 (13)
Figure 2
Figure 2
Recombination-dependent interstrand crosslink repair pathway in vertebrates. This pathway includes initiation, unhooking, SNMA1 digestion, translesion synthesis, nucleotide excision, gap filling, and homologous recombination. Note, this model is adapted from the one proposed by Raschle, M. et al. in 2008 (23). In their study, however, SNM1A digestion is not required. Instead, as the green-arrowed strands indicated, the new strand is extended to one base ahead of the lesion site before excision occurs. After unhooking, Rev1 inserts a cytosine into the position across the lesion on the complementary strand. Then Pol ζ, the key translesion polymerase, processes the DNA synthesis beyond the lesion site
Figure 3
Figure 3
Recombination-independent interstrand crosslink repair pathway in vertebrates. This pathway includes initiation, unhooking, translesion synthesis, nucleotide excision, and gap filling. Note, this model is adapted from the one proposed by Zheng H. et al. in 2003 (28)
See this image and copyright information in PMC

References

    1. O'Donovan A, Davies AA, Moggs JG, et al. XPG endonuclease makes the 3' incision in human DNA nucleotide excision repair. Nature. 1994;371:432–435. - PubMed
    1. Goodman LS, Wintrobe MM. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J Am Med Assoc. 1946;132:126–132. - PubMed
    1. McVey M. Strategies for DNA interstrand crosslink repair: insights from worms, flies, frogs, and slime molds. Environ Mol Mutagen. 2010;51:646–658. - PubMed
    1. Noll DM, Mason TM, Miller PS. Formation and repair of interstrand cross-links in DNA. Chem Rev. 2006;106:277–301. - PMC - PubMed
    1. Lawley PD, Phillips DH. DNA adducts from chemotherapeutic agents. Mutat Res. 1996;355:13–40. - PubMed