Structure determination of DNA methylation lesions N¹-meA and N³-meC in duplex DNA using a cross-linked protein-DNA system

Journal Article · Fri Aug 13 00:00:00 EDT 2010 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkq129· OSTI ID:1002593

Lu, Lianghua; Yi, Chengqi; Jian, Xing; Zheng, Guanqun; He, Chuan ^[1]

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1. UC

N¹-meA and N³-meC are cytotoxic DNA base methylation lesions that can accumulate in the genomes of various organisms in the presence of S_N2 type methylating agents. We report here the structural characterization of these base lesions in duplex DNA using a cross-linked protein-DNA crystallization system. The crystal structure of N¹-meA:T pair shows an unambiguous Hoogsteen base pair with a syn conformation adopted by N¹-meA, which exhibits significant changes in the opening, roll and twist angles as compared to the normal A:T base pair. Unlike N¹-meA, N³-meC does not establish any interaction with the opposite G, but remains partially intrahelical. Also, structurally characterized is the N⁶-meA base modification that forms a normal base pair with the opposite T in duplex DNA. Structural characterization of these base methylation modifications provides molecular level information on how they affect the overall structure of duplex DNA. In addition, the base pairs containing N¹-meA or N³-meC do not share any specific characteristic properties except that both lesions create thermodynamically unstable regions in a duplex DNA, a property that may be explored by the repair proteins to locate these lesions.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1002593
• Journal Information: Nucleic Acids Research, Vol. 38, Issue (13) ; 07, 2010; ISSN 0305-1048
• Publisher: Oxford University Press
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
CRYSTALLIZATION
DNA
METHYLATION
MODIFICATIONS
PROTEINS
REPAIR