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Poly(ADP‐ribose) polymerase‐1 promotes recruitment of meiotic recombination‐11 to chromatin and DNA double‐strand break repair in Ku70‐deficient breast cancer cells
Author(s) -
Huang Yujing,
Shao Qing,
Luo Xinrong,
Yang Dejuan,
Zeng Beilei,
Xiang Tingxiu,
Ren Guosheng,
Cheng Qiao
Publication year - 2018
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/fj.201800092r
Subject(s) - ku70 , chromatin , poly adp ribose polymerase , dna repair , biology , microbiology and biotechnology , homologous recombination , polymerase , dna , genetics
Poly(ADP‐ribose) polymerase (PARP)‐1 may act in an error‐prone pathway called alternative end joining (Alt‐EJ) for DNA double‐strand break (DSB) repair when nonhomologous end joining is defective. We examined the recruitment of PARP‐1 to chromatin in response to radiomimetic agents and the effects of PARP‐1 inhibition on DSB repair and recruitment of the meiotic recombination (MRE)‐11‐double‐strand break repair (RAD50) protein‐Nijmegen breakage syndrome (NSB)‐1 (MRN) complex to the chromatin in Ku70‐deficient breast cancer cells. The chromatin‐binding affinity of PARP‐1 was enhanced in response to neocarzinostatin (NCS) or ca‐ licheamicin treatment in the absence of Ku70. PARP‐1 inhibition impaired the repair of both NCS‐induced DSBs and intron‐encoded endonuclease from Physarumpolycephalum‐induced site‐specific DSB. Both fractionation and chromatin immunoprecipitation assays demonstrated that chromatin recruitment of MRN was PARP‐1 dependent. These data suggest that PARP‐1 is vital for DSB repair in breast cancer cells when Alt‐EJ is activated.—Huang, Y., Shao, Q., Luo, X., Yang, D., Zeng, B., Xiang, T., Ren, G., Cheng, Q. Poly(ADP‐ribose) polymerase‐1 promotes recruitment of meiotic recombination‐11 to chromatin and DNA double‐strand break repair in Ku70‐deficient breast cancer cells. FASEB J . 32, 6112–6122 (2018). www.fasebj.org