DNA-PK-Dependent RPA2 Hyperphosphorylation Facilitates DNA Repair and Suppresses Sister Chromatid Exchange
2011

How RPA2 Hyperphosphorylation Affects DNA Repair

publication Evidence: high

Author Information

Author(s): Liaw Hungjiun, Lee Deokjae, Myung Kyungjae

Primary Institution: National Human Genome Research Institute, National Institutes of Health

Hypothesis

What types of DNA lesions cause RPA2 hyperphosphorylation, which kinase(s) are responsible for them, and what is the biological outcome of these phosphorylations?

Conclusion

RPA2 hyperphosphorylation by DNA-PK in response to DNA double-strand breaks blocks unscheduled homologous recombination and delays mitotic entry.

Supporting Evidence

  • RPA2 hyperphosphorylation occurs primarily in response to genotoxic stresses that cause high levels of DNA double-strand breaks.
  • DNA-PK is responsible for the modifications of RPA2 in vivo.
  • Alteration of RPA2 to prevent phosphorylation at specific sites caused increased mitotic entry and homologous recombination.

Takeaway

When cells get damaged, a protein called RPA2 gets a special tag that helps fix the damage and makes sure the cell doesn't divide too soon.

Methodology

The study involved treating HEK293T cells with various DNA damaging agents and monitoring RPA2 phosphorylation.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0021424

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