Open AccessFork-like DNA templates support bypass replication of lesions that block DNA synthesis on single-stranded templates
Author(s) -
Jean-Sébastien Hoffmann,
Marie-Jeanne Pillaire,
Claire Lesca,
Dominique Burnouf,
Robert Fuchs,
Martine Defais,
Giuseppe Villani
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.24.13766
Subject(s) - dna replication , dna , dna synthesis , dna polymerase , biology , dna clamp , proliferating cell nuclear antigen , dna polymerase ii , eukaryotic dna replication , control of chromosome duplication , microbiology and biotechnology , biochemistry , chemistry , gene , polymerase chain reaction , reverse transcriptase
DNA replication is an asymmetric process involving concurrent DNA synthesis on leading and lagging strands. Leading strand synthesis proceeds concomitantly with fork opening, whereas synthesis of the lagging strand essentially takes place on a single-stranded template. The effect of this duality on DNA damage processing by the cellular replication machinery was tested using eukaryotic cell extracts and model DNA substrates containing site-specific DNA adducts formed by the anticancer drug cisplatin or by the carcinogen N-2-acetylaminofluorene. Bypass of both lesions was observed only with fork-like substrates, whereas complete inhibition of DNA synthesis occurred on damaged single-stranded DNA substrates. These results suggest a role for additional accessory factors that permit DNA polymerases to bypass lesions when present in fork-like DNA.