Cdk1 Restrains NHEJ through Phosphorylation of XRCC4-like Factor Xlf1

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Cdk1 Restrains NHEJ through Phosphorylation of XRCC4-like Factor Xlf1

Eukaryotic cells use two principal mechanisms for repairing DNA double-strand breaks (DSBs): homologous recombination (HR) and nonhomologous end-joining (NHEJ). DSB repair pathway choice is strongly regulated during the cell cycle. Cyclin-dependent kinase 1 (Cdk1) activates HR by phosphorylation of key recombination factors. However, a mechanism for regulating the NHEJ pathway has not been esta...

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Mutations in the NHEJ component XRCC4 cause primordial dwarfism.

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mut...

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XRCC4-like factor (XLF) is involved in non-homologous end joining-mediated repair of DNA double-strand breaks (DSBs). Mutations in the WRN gene results in the development of Werner syndrome (WS), a rare autosomal recessive disorder characterized by premature ageing and genome instability. In the present study, it was identified that XLF protein levels were lower in WRN-deficient fibroblasts, co...

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Role of XRCC4 and XLF in NHEJ Resolving how XRCC4 and XLF interact with DNA and what functions

Non-Homologous End Joining (NHEJ) is an efficient mechanism to repair DNA double-strand breaks. XRCC4 and XLF are two structurally-similar core NHEJ proteins. They can directly interact at the protein-protein level and engage DNA by an unknown mechanism. Here, we use optical tweezers and fluorescence microscopy to visualize XRCC4XLF complexes on DNA in real time. We find that the behavior of XR...

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ژورنال

عنوان ژورنال: Cell Reports

سال: 2014

ISSN: 2211-1247

DOI: 10.1016/j.celrep.2014.11.044