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A new sub‐pathway of long‐patch base excision repair involving 5′ gap formation
Author(s) -
Woodrick Jordan,
Gupta Suhani,
Camacho Sharon,
Parvathaneni Swetha,
Choudhury Sujata,
Cheema Amrita,
Bai Yi,
Khatkar Pooja,
Erkizan Hayriye Verda,
Sami Furqan,
Su Yan,
Schärer Orlando D,
Sharma Sudha,
Roy Rabindra
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694920
Subject(s) - base excision repair , biology , dna repair , dna damage , nucleotide excision repair , helicase , dna glycosylase , poly adp ribose polymerase , dna , ap endonuclease , microbiology and biotechnology , dna polymerase beta , ap site , polymerase , genetics , gene , rna
Base excision repair ( BER ) is one of the most frequently used cellular DNA repair mechanisms and modulates many human pathophysiological conditions related to DNA damage. Through live cell and in vitro reconstitution experiments, we have discovered a major sub‐pathway of conventional long‐patch BER that involves formation of a 9‐nucleotide gap 5′ to the lesion. This new sub‐pathway is mediated by RECQ 1 DNA helicase and ERCC 1‐ XPF endonuclease in cooperation with PARP 1 poly( ADP ‐ribose) polymerase and RPA . The novel gap formation step is employed during repair of a variety of DNA lesions, including oxidative and alkylation damage. Moreover, RECQ 1 regulates PARP 1 auto‐( ADP ‐ribosyl)ation and the choice between long‐patch and single‐nucleotide BER , thereby modulating cellular sensitivity to DNA damage. Based on these results, we propose a revised model of long‐patch BER and a new key regulation point for pathway choice in BER .