Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

2008 ◽  
Vol 646 (1-2) ◽  
pp. 8-16 ◽  
Author(s):  
Marcelo de Campos-Nebel ◽  
Irene Larripa ◽  
Marcela González-Cid
Keyword(s):  
Mammalian Cells ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Non Homologous End Joining

scholarly journals Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining

2009 ◽  
Vol 417 (3) ◽  
pp. 639-650 ◽  
Author(s):  
Brandi L. Mahaney ◽  
Katheryn Meek ◽  
Susan P. Lees-Miller
Keyword(s):  
Ionizing Radiation ◽  
Mammalian Cells ◽  
Chinese Hamster ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Dna Lesion ◽  
Topoisomerase Poisons ◽  
Non Homologous End Joining

DNA DSBs (double-strand breaks) are considered the most cytotoxic type of DNA lesion. They can be introduced by external sources such as IR (ionizing radiation), by chemotherapeutic drugs such as topoisomerase poisons and by normal biological processes such as V(D)J recombination. If left unrepaired, DSBs can cause cell death. If misrepaired, DSBs may lead to chromosomal translocations and genomic instability. One of the major pathways for the repair of IR-induced DSBs in mammalian cells is NHEJ (non-homologous end-joining). The main proteins required for NHEJ in mammalian cells are the Ku heterodimer (Ku70/80 heterodimer), DNA-PKcs [the catalytic subunit of DNA-PK (DNA-dependent protein kinase)], Artemis, XRCC4 (X-ray-complementing Chinese hamster gene 4), DNA ligase IV and XLF (XRCC4-like factor; also called Cernunnos). Additional proteins, including DNA polymerases μ and λ, PNK (polynucleotide kinase) and WRN (Werner's Syndrome helicase), may also play a role. In the present review, we will discuss our current understanding of the mechanism of NHEJ in mammalian cells and discuss the roles of DNA-PKcs and DNA-PK-mediated phosphorylation in NHEJ.

scholarly journals Genetic dissection of vertebrate 53BP1: A major role in non-homologous end joining of DNA double strand breaks

DNA Repair ◽  
2006 ◽  
Vol 5 (6) ◽  
pp. 741-749 ◽  
Author(s):  
Kyoko Nakamura ◽  
Wataru Sakai ◽  
Takuo Kawamoto ◽  
Ronan T. Bree ◽  
Noel F. Lowndes ◽  
...  
Keyword(s):  
Double Strand Breaks ◽  
Genetic Dissection ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Non Homologous End Joining

scholarly journals Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs

2018 ◽  
Author(s):  
Roopa Thapar
Keyword(s):  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Dna Double Strand Break ◽  
Protein Dna Interactions ◽  
Damage Response ◽  
Non Coding Rnas ◽  
Non Homologous End Joining

DNA double-strand breaks (DSBs) are deleterious lesions that are generated in response to ionizing radiation or replication fork collapse that can lead to genomic instability and cancer.  Eukaryotes have evolved two major pathways, namely homologous recombination (HR) and non-homologous end joining (NHEJ) to repair DSBs.  Whereas the roles of protein-DNA interactions in HR and NHEJ have been fairly well defined, the functions of small and long non-coding RNAs and RNA-DNA hybrids in the DNA damage response is just beginning to be elucidated.  This review summarizes recent discoveries on the identification of non-coding RNAs and RNA-mediated regulation of DSB repair

scholarly journals CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Magdalena B. Rother ◽  
Stefania Pellegrino ◽  
Rebecca Smith ◽  
Marco Gatti ◽  
Cornelia Meisenberg ◽  
...  
Keyword(s):  
Charge Syndrome ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Dsb Repair ◽  
Strand Breaks ◽  
Multiple Levels ◽  
Non Homologous End Joining ◽  
And Shifts ◽  
Chromatin Relaxation

AbstractChromatin structure is dynamically reorganized at multiple levels in response to DNA double-strand breaks (DSBs). Yet, how the different steps of chromatin reorganization are coordinated in space and time to differentially regulate DNA repair pathways is insufficiently understood. Here, we identify the Chromodomain Helicase DNA Binding Protein 7 (CHD7), which is frequently mutated in CHARGE syndrome, as an integral component of the non-homologous end-joining (NHEJ) DSB repair pathway. Upon recruitment via PARP1-triggered chromatin remodeling, CHD7 stimulates further chromatin relaxation around DNA break sites and brings in HDAC1/2 for localized chromatin de-acetylation. This counteracts the CHD7-induced chromatin expansion, thereby ensuring temporally and spatially controlled ‘chromatin breathing’ upon DNA damage, which we demonstrate fosters efficient and accurate DSB repair by controlling Ku and LIG4/XRCC4 activities. Loss of CHD7-HDAC1/2-dependent cNHEJ reinforces 53BP1 assembly at the damaged chromatin and shifts DSB repair to mutagenic NHEJ, revealing a backup function of 53BP1 when cNHEJ fails.

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