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Hot Paper in the Biochemical Journal
September 20, 2002DNA DAMAGE INSIGHT
An exciting new paper from the Biochemical Journal regarding the phosphorylation state of LKB1 in response to ionising radiation can be viewed online as an Immediate Publication at www.BiochemJ.org (DOI: 10.1042/BJ20021284).
Researchers at the University of Dundee, the University of Calgary and Tel Aviv University collaborated on the work, which demonstrates a role for ataxia telangiectasia mutated kinase (ATM) in mediating the phosphorylation of the tumour suppressor serine threonine protein kinase LKB1, that is mutated in the inherited Peutz Jeghers cancer syndrome.
ATM is a master sensor of DNA damage, ensuring that when DNA damage occurs, cell division is immediately halted until the damage is repaired. Mutations in ATM that inactivate this kinase lead to cancer predisposition as these cells are thought to undergo cell division before any DNA damage can be repaired. ATM is activated in cells by double stranded DNA breaks induced by ionising radiation, and halts cell division by phosphorylating proteins that regulate the cell cycle. It is likely that many of the cellular ATM substrates have not yet been discovered.
LKB1 regulates cell growth by an unknown mechanism. It was previously demonstrated by the same researchers that LKB1 was phosphorylated in cells at a specific threonine residue. As a next step to understand the importance of this phosphorylation, they developed an antibody to this phosphorylated form of LKB1 and demonstrated that exposure of cells to ionising radiation induced a marked phosphorylation of this threonine residue. Excitingly, the authors demonstrate that in cells lacking ATM, ionising radiation no longer induces phosphorylation of LKB1 and also show that LKB1 is efficiently phosphorylated by ATM in vitro.
"The results of this study provide the first link between ATM and LKB1, two protein kinases involved in regulating cell proliferation," says Gopal Sapkota (Dundee) "This is a potentially important finding that indicates that LKB1 could mediate some of the DNA damage check-point control processes that are triggered by ATM. This research will stimulate future work to identify the mechanism by which LKB1 regulates cell growth and how this could regulate DNA damage and repair pathways."
Fraunhofer-Gesellschaft
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Plants display 'molecular amnesia'
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Tool Helps Identify Gene Function in Soybeans, Could Lead to Better Crop Performance, say MU Researchers
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Ice beetles impacted by climate change
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Fruit fly research may lead to better understanding of human heart disease
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CSHL scientists discover a new way in which epigenetic information is inherited
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Synthetic virus supports a bat origin for SARS
SARS - severe acute respiratory syndrome - alarmed the world five years ago as the first global pandemic of the 21st century. The coronavirus (SARS-CoV) that sickened more than 8,000 people - and killed nearly 800 of them - may have originated in bats, but the actual animal source is not known.
Scripps Research Scientists Shed Light on How DNA Is Unwound So That Its Code Can Be Read
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