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preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 4

The DNA Helicase Recql4 Is Required for Normal Osteoblast Expansion and Osteosarcoma Formation

English version České info

Rothmund Thomson Syndrome (RTS), RAPADILINO Syndrome and Baller-Gerold Syndrome are very rare human syndromes associated with mutations in RECQL4. RECQL4 is important for controlling how cells divide and for preventing genome damage. Patients with RECQL4 mutations have problems with bone formation and a low bone mass, similar to osteoporosis. RTS patients have a highly increased risk of developing bone cancer (osteosarcoma). The role of RECQL4 in normal bone development and osteosarcoma formation is largely unknown. We have used mouse models to understand the specific role of Recql4 in bone development. Mice with Recql4 removed specifically from their bone cells have shortened bones and a reduced rate of bone formation. Therefore, RECQL4 is essential for normal bone development. Interestingly, the animals with no Recql4 in bone cells did not develop osteosarcoma. Using mouse models of osteosarcoma, we observed delayed cancer formation when Recql4 was also deleted. Further analysis demonstrated that bone cancer could not arise from Recql4 null cells even with concurrent p53 deletion. These studies clarify the role of RECQL4 in both normal and malignant bone biology and suggest that RECQL4 mutations that cause osteosarcoma most likely result in proteins with reduced, but not absent, function.

Vyšlo v časopise: The DNA Helicase Recql4 Is Required for Normal Osteoblast Expansion and Osteosarcoma Formation. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005160
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005160

Souhrn

Rothmund Thomson Syndrome (RTS), RAPADILINO Syndrome and Baller-Gerold Syndrome are very rare human syndromes associated with mutations in RECQL4. RECQL4 is important for controlling how cells divide and for preventing genome damage. Patients with RECQL4 mutations have problems with bone formation and a low bone mass, similar to osteoporosis. RTS patients have a highly increased risk of developing bone cancer (osteosarcoma). The role of RECQL4 in normal bone development and osteosarcoma formation is largely unknown. We have used mouse models to understand the specific role of Recql4 in bone development. Mice with Recql4 removed specifically from their bone cells have shortened bones and a reduced rate of bone formation. Therefore, RECQL4 is essential for normal bone development. Interestingly, the animals with no Recql4 in bone cells did not develop osteosarcoma. Using mouse models of osteosarcoma, we observed delayed cancer formation when Recql4 was also deleted. Further analysis demonstrated that bone cancer could not arise from Recql4 null cells even with concurrent p53 deletion. These studies clarify the role of RECQL4 in both normal and malignant bone biology and suggest that RECQL4 mutations that cause osteosarcoma most likely result in proteins with reduced, but not absent, function.

Zdroje

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