Embryonic lethality after combined inactivation of Fancd2 and Mlh1 in mice.

Cancer Research
H J van de VrugtMarkus Grompe

Abstract

DNA repair defects are frequently encountered in human cancers. These defects are utilized by traditional therapeutics but also offer novel cancer treatment strategies based on synthetic lethality. To determine the consequences of combined Fanconi anemia (FA) and mismatch repair pathway inactivation, defects in Fancd2 and Mlh1 were combined in one mouse model. Fancd2/Mlh1 double-mutant embryos displayed growth retardation resulting in embryonic lethality and significant underrepresentation among progeny. Additional inactivation of Trp53 failed to improve the survival of Fancd2/Mlh1-deficient embryos. Mouse fibroblasts were obtained and challenged with cross-linking agents. Fancd2-deficient cells displayed the FA-characteristic growth inhibition after mitomycin C (MMC) exposure. In primary fibroblasts, the absence of Mlh1 did not greatly affect the MMC sensitivity of Fancd2-deficient and Fancd2-proficient cells. However, in Trp53 mutant immortalized fibroblasts, Mlh1 deficiency reduced the growth-inhibiting effect of MMC in Fancd2 mutant and complemented cells. Similar data were obtained using psoralen/UVA, signifying that MLH1 influences the cellular sensitivity to DNA interstrand cross-links. Next, the effect of MLH1 deficienc...Continue Reading

References

Apr 8, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·H J van de VrugtF Arwert
Mar 10, 2001·Molecular Cell·C TimmersM Grompe
May 18, 2001·Nature·J H Hoeijmakers
Jun 28, 2001·The Journal of Biological Chemistry·C SchmutteR Fishel
Dec 26, 2001·Molecular Genetics and Metabolism·Y M AkkariM Grompe
Feb 2, 2002·Human Molecular Genetics·Mireille KoomenFré Arwert
Mar 29, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Henri J van de VrugtFré Arwert
May 2, 2003·Molecular and Cellular Biology·Amom Ruhikanta MeeteiWeidong Wang
Aug 2, 2003·Genes & Development·Scott HoughtalingMarkus Grompe
Oct 14, 2004·Oncogene·Changshun ShaoJay A Tischfield
Dec 27, 2005·Cell·Laura J NiedernhoferJan H J Hoeijmakers
Feb 21, 2006·Cell·Xuewen PanJef D Boeke
May 2, 2006·Molecular Cancer Therapeutics·Deborah ChirnomasAlan D D'Andrea
Jun 13, 2006·Cancer Cell·Jean Y J Wang, Winfried Edelmann
Jul 29, 2006·Cell·Farid A KadyrovPaul Modrich
May 10, 2007·Developmental Cell·Markus Grompe, Henri van de Vrugt
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lainie P MartinRussell J Schilder
Mar 18, 2008·Current Opinion in Genetics & Development·Sarah A MartinAlan Ashworth
Apr 11, 2008·Phytochemical Analysis : PCA·Laura BissonnetteMyron L Smith
Apr 29, 2008·Current Opinion in Genetics & Development·Lisa M Coussens, Tyler Jacks

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.