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Understanding base lesion DNA repair (477.2)
Author(s) -
Wilson Samuel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.477.2
Subject(s) - base excision repair , dna repair , dna polymerase beta , poly adp ribose polymerase , xrcc1 , polymerase , dna polymerase , proliferating cell nuclear antigen , dna , biology , microbiology and biotechnology , context (archaeology) , dna clamp , chemistry , biochemistry , polymerase chain reaction , gene , reverse transcriptase , paleontology , genotype , single nucleotide polymorphism
The mammalian DNA repair pathway for small base lesions involves excision of the damaged base, DNA synthesis to fill the excision gap and gap‐trimming steps to prepare substrates for downstream enzymes, including DNA ligases. The topic of DNA base excision repair (BER) will be reviewed, along with the hypothesis of “substrate‐channeling” of repair intermediates from one step to the next step until the repair process has been completed. The accessory proteins XRCC1 and PARP‐1 play important roles in BER, and these proteins and the BER enzymes appear to function in large macromolecular complexes. In the case of PARP‐1, poly(ADP‐ribose) adduction of itself and other BER enzymes facilitates recruitment to the repair complex. The catalytic cycle of DNA polymerase beta is relevant to the substrate‐channeling hypothesis because the enzyme plays a central role in BER. Crystal structures of human DNA polymerase beta will be discussed in the context of the catalytic cycle of polymerase beta and the substrate‐channeling hypothesis.