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Human DNA polymerases (pols) beta and lambda could promote template slippage and generate -1 frameshifts on defined heteropolymeric DNA substrates containing a single abasic site. Kinetic data demonstrated that pol lambda was more efficient than pol beta in catalyzing translesion DNA synthesis past an abasic site, particularly in the presence of low nucleotide concentrations. Moreover, pol lambda was found to generate frameshifts in two ways: first, by using a nucleotide-stabilized primer misalignment mechanism, or second, by promoting primer reannealing using microhomology regions between the terminal primer sequence and the template strand. Our results suggest a molecular mechanism for the observed high in vivo rate of frameshifts generation by pol lambda and highlight the remarkable ability of pol lambda to promote microhomology pairing between two DNA strands, further supporting its proposed role in the nonhomologous end joining process.

Original publication

DOI

10.1021/bi049050x

Type

Journal article

Journal

Biochemistry

Publication Date

14/09/2004

Volume

43

Pages

11605 - 11615

Keywords

Base Sequence, DNA Damage, DNA Polymerase beta, DNA Primers, DNA Repair, DNA Replication, DNA-(Apurinic or Apyrimidinic Site) Lyase, Frameshift Mutation, Furans, Humans, Kinetics, Repetitive Sequences, Nucleic Acid, Substrate Specificity, Templates, Genetic