ATM and ATR Activities Maintain Replication Fork Integrity during SV40 Chromatin Replication

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ATM and ATR Activities Maintain Replication Fork Integrity during SV40 Chromatin Replication

Mutation of DNA damage checkpoint signaling kinases ataxia telangiectasia-mutated (ATM) or ATM- and Rad3-related (ATR) results in genomic instability disorders. However, it is not well understood how the instability observed in these syndromes relates to DNA replication/repair defects and failed checkpoint control of cell cycling. As a simple model to address this question, we have studied SV40...

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ATR and ATM differently regulate WRN to prevent DSBs at stalled replication forks and promote replication fork recovery.

Accurate response to replication arrest is crucial to preserve genome stability and requires both the ATR and ATM functions. The Werner syndrome protein (WRN) is implicated in the recovery of stalled replication forks, and although an ATR/ATM-dependent phosphorylation of WRN was observed after replication arrest, the function of such modifications during the response to perturbed replication is...

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ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling.

The phosphatidyl inositol 3-kinase-like kinases (PIKKs), ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) regulate parallel damage response signalling pathways. ATM is reported to be activated by DNA double-strand breaks (DSBs), whereas ATR is recruited to single-stranded regions of DNA. Although the two pathways were considered to function independently, recent studies have ...

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Chromatin assembly controls replication fork stability.

During DNA replication, the advance of replication forks is tightly connected with chromatin assembly, a process that can be impaired by the partial depletion of histone H4 leading to recombinogenic DNA damage. Here, we show that the partial depletion of H4 is rapidly followed by the collapse of unperturbed and stalled replication forks, even though the S-phase checkpoints remain functional. Th...

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ATR phosphorylates SMARCAL1 to prevent replication fork collapse.

The DNA damage response kinase ataxia telangiectasia and Rad3-related (ATR) coordinates much of the cellular response to replication stress. The exact mechanisms by which ATR regulates DNA synthesis in conditions of replication stress are largely unknown, but this activity is critical for the viability and proliferation of cancer cells, making ATR a potential therapeutic target. Here we use sel...

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ژورنال

عنوان ژورنال: PLoS Pathogens

سال: 2013

ISSN: 1553-7374

DOI: 10.1371/journal.ppat.1003283