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ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation
TLDR
It is shown that under most normal growth conditions, IR-induced H2AX phosphorylation can be carried out by ATM and DNA-PK in a redundant, overlapping manner. Expand
ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin.
TLDR
It is shown that < or =25% of DSBs require ATM signaling for repair, and this percentage correlates with increased chromatin but not damage complexity, which suggests that the importance of ATM signalling for DSB repair increases as the heterochromatic component of a genome expands. Expand
A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci.
TLDR
It is shown that ataxia telangiectasia mutated protein (ATM) and Artemis, the protein defective in patients with RS-SCID, function in a common double-strand break repair pathway that also requires H2AX, 53BP1, Nbs1, Mre11, and DNA-PK. Expand
A splicing mutation affecting expression of ataxia–telangiectasia and Rad3–related protein (ATR) results in Seckel syndrome
TLDR
This analysis shows that UV-induced ATR activation can occur in non-replicating cells following processing by nucleotide excision repair, and identifies a synonymous mutation in affected individuals that alters ATR splicing. Expand
The role of double-strand break repair — insights from human genetics
TLDR
Understanding of the molecular basis that underlies the diverse clinical features of human disorders with pleiotropic clinical features is enhancing the understanding of the damage-response mechanisms and their role in development, and might ultimately facilitate treatment. Expand
γH2AX foci analysis for monitoring DNA double-strand break repair: Strengths, limitations and optimization
TLDR
Evidence is presented that following exposure to ionising radiation, γH2AX foci analysis can provide a sensitive monitor of DSB formation and repair and techniques to optimise the analysis are described, enabling the procedure to be optimally exploited but not misused. Expand
DNA‐PK autophosphorylation facilitates Artemis endonuclease activity
TLDR
It is proposed that autophosphorylation triggers conformational changes in DNA‐PK that enhance Artemis cleavage at single‐strand to double‐stranded DNA junctions, providing insight into the mechanism of Artemis mediated DNA end processing. Expand
Factors determining DNA double‐strand break repair pathway choice in G2 phase
TLDR
It is proposed that NHEJ initially attempts to repair DSBs and, if rapid rejoining does not ensue, then resection occurs promoting repair by HR, and novel roles for ATM in regulating DSB end resection are identified. Expand
Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation
TLDR
It is demonstrated that yeast artificial chromosomes containing the DNA- PKcs gene complement both the DNA repair and recombination deficiencies of V3 cells, and it is concluded that DNA-PKcs is encoded by the XRCC7 gene. Expand
The impact of a negligent G2/M checkpoint on genomic instability and cancer induction
TLDR
The impact of a negligent G2/M checkpoint on genomic stability and cancer risk is considered and a defined threshold of 10–20 DSBs is shown. Expand
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