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Direct role for the replication protein treslin (Ticrr) in the ATR kinase-mediated checkpoint response

Bachar H Hassan1, Laura A Lindsey-Boltz, Michael G Kemp

  • 1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260, USA.

The Journal of Biological Chemistry
|May 23, 2013
PubMed

Insights

Treslin is a dual replication and checkpoint protein. It stimulates ATR phosphorylation of Chk1, a key step in DNA damage response, in a manner dependent on TopBP1.

Area of Science:

  • Cellular biology
  • Molecular biology
  • DNA replication and repair

Background:

  • Topoisomerase IIβ-binding protein 1 (TopBP1) is a known dual-function protein involved in DNA replication and checkpoint control.
  • Treslin (also known as Ticrr) is an essential replication protein identified as a binding partner of TopBP1 and a regulator in zebrafish checkpoint pathways.
  • While Treslin's role in DNA replication initiation is partially understood, its function in checkpoint responses remains unclear.

Purpose of the Study:

  • To investigate the role of Treslin in DNA damage checkpoint signaling.
  • To determine if Treslin participates in ATR-mediated phosphorylation of Chk1.
  • To elucidate the contribution of Treslin's phosphorylation state to its checkpoint activity.

Main Methods:

  • In vitro and in vivo biochemical assays.
  • Analysis of Treslin phosphorylation at Ser-1000.
  • TopBP1-dependent assays.

Main Results:

  • Treslin was shown to stimulate ATR phosphorylation of Chk1 both in vitro and in vivo.
  • This Treslin-mediated stimulation of Chk1 phosphorylation is dependent on TopBP1.
  • Phosphorylation of Treslin at Ser-1000 was found to be critical for its checkpoint function.

Conclusions:

  • Treslin functions as a dual-acting protein, participating in both DNA replication and checkpoint control, similar to TopBP1.
  • Treslin directly contributes to ATR-mediated DNA damage checkpoint signaling.
  • The phosphorylation status of Treslin, particularly at Ser-1000, is crucial for its role in checkpoint activation.
Keywords:
CDK (Cyclin-dependent Kinase)Cell SignalingCheckpointCheckpoint ControlChk1DNA DamagePhosphorylationTopBP1

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