Crosslinking of DNA

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In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two different positions in the DNA. This can either occur in the same strand (intrastrand crosslink) or in the opposite strands of the DNA (interstrand crosslink). Crosslinks also occur between DNA and protein. DNA replication is blocked by crosslinks, which causes replication arrest and cell death if the crosslink is not repaired.

The RAD51 family plays a role in repair.[1]

Crosslinking agents[edit]


Alkylating agents such as 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine)) and nitrogen mustard which are used in chemotherapy can cross link with DNA at N7 position of guanine on the opposite strands forming interstrand crosslink.[2]

Cisplatin (cis-diamminedichloroplatinum(II)) and its derivatives forms DNA cross links as monoadduct, interstrand crosslink, intrastrand crosslink or DNA protein crosslink. Mostly it acts on the adjacent N-7 guanine forming 1, 2 intrastrand crosslink.[3][4]

DNA damage can be induced by ionizing radiation is similar to oxidative stress, and these lesions have been implicated in aging and cancer. Biological effects of single-base damage by radiation or oxidation, such as 8-oxoguanine and thymine glycol, have been extensively studied. Recently has the focus shifted to some of the more complex lesions. Tandem DNA lesions are formed at substantial frequency by ionizing radiation and metal-catalyzed H2O2 reactions. Under anoxic conditions, the predo-minant double-base lesion is a species in which C8 of guanine is linked to the 5-methyl group of an adjacent 3'-thymine (G[8,5- Me]T). [5]



  1. ^ Gruver AM, Miller KA, Rajesh C, et al. (November 2005). "The ATPase motif in RAD51D is required for resistance to DNA interstrand crosslinking agents and interaction with RAD51C". Mutagenesis 20 (6): 433–40. doi:10.1093/mutage/gei059. PMID 16236763. 
  2. ^ Ali-Osman F, Rairkar A, Young P (January 1995). "Formation and repair of 1,3-bis-(2-chloroethyl)-1-nitrosourea and cisplatin induced total genomic DNA interstrand crosslinks in human glioma cells". Cancer Biochem. Biophys. 14 (4): 231–41. PMID 7767897. 
  3. ^ Poklar N, Pilch DS, Lippard SJ, Redding EA, Dunham SU, Breslauer KJ (July 1996). "Influence of cisplatin intrastrand crosslinking on the conformation, thermal stability, and energetics of a 20-mer DNA duplex". Proc. Natl. Acad. Sci. U.S.A. 93 (15): 7606–11. doi:10.1073/pnas.93.15.7606. PMC 38793. PMID 8755522. 
  4. ^ Rudd GN, Hartley JA, Souhami RL (1995). "Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood mononuclear cells from elderly and young individuals". Cancer Chemother. Pharmacol. 35 (4): 323–6. doi:10.1007/BF00689452. PMID 7828275. 
  5. ^ LC Colis, P Raychaudhury, AK Basu (2008). "Mutational specificity of gamma-radiation-induced guanine-thymine and thymine-guanine intrastrand cross-links in mammalian cells and translesion synthesis past the guanine-thymine lesion by human DNA polymerase eta". Biochemistry 47 (6): 8070–8079. doi:10.1021/bi800529f. PMID 18616294. 
  6. ^ Mathews & Vanholde, Biochemistry, 2nd Edition. Benjamin Cummings Publication
  7. ^ Qi Wu, Laura A Christensen, Randy J Legerski & Karen M Vasquez, Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells,EMBO reports 6, 6, 551–557 (2005).
  8. ^ Formaldehyde Crosslinking Experiments [1]
  9. ^ Somashe Niranjanakumaria, Erika Lasdaa, Robert Brazasa, Mariano A. Garcia-Blanco. Reversible cross-linking combined with immunoprecipitation to study RNA–protein interactions in vivo. Methods. 2002 Feb;26(2):182-90. [2]

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