Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 calicheamicin treatment in the absence of Ku70. PARP-1 inhibition impaired the repair of both NCS-induced DSBs and intron-encoded endonuclease from Physarum polycephalum-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.
 ...
PMID: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. 2987 27

An important but still enigmatic function of DNA:RNA hybrids is their role in DNA double-strand break (DSB) repair. Here, we show that Sen1, the budding yeast ortholog of the human helicase Senataxin, is recruited at an HO endonuclease-induced DSB and limits the local accumulation of DNA:RNA hybrids. In the absence of Sen1, hybrid accumulation proximal to the DSB promotes increased binding of the Ku70-80 (KU) complex at the break site, mutagenic non-homologous end joining (NHEJ), micro-homology-mediated end joining (MMEJ), and chromosome translocations. We also show that homology-directed recombination (HDR) by gene conversion is mostly proficient in sen1 mutants after single DSB. However, in the absence of Sen1, DNA:RNA hybrids, Mre11, and Dna2 initiate resection through a non-canonical mechanism. We propose that this resection mechanism through local DNA:RNA hybrids acts as a backup to prime HDR when canonical pathways are altered, but at the expense of genome integrity.
 ...
PMID:Senataxin Ortholog Sen1 Limits DNA:RNA Hybrid Accumulation at DNA Double-Strand Breaks to Control End Resection and Repair Fidelity. 3237 52


<< Previous 1 2 3