Info

motif [9'12]

bFor nomenclature rules of FA gene symbols, see http://www.gene.ucl.ac.uk/nomenclature/genefamily/fanconi.html. cThese genes remain to be identified.

The proteins defective in these groups act downstream of the monoubiquitination of FANCD2; all the other FA proteins listed act upstream.

bFor nomenclature rules of FA gene symbols, see http://www.gene.ucl.ac.uk/nomenclature/genefamily/fanconi.html. cThese genes remain to be identified.

The proteins defective in these groups act downstream of the monoubiquitination of FANCD2; all the other FA proteins listed act upstream.

-A, -G, -F and -E were identified by complementation cloning;[2,5] FANCA was independently found by linkage analysis and positional cloning[6] FANCD2 by mi-crocell-mediated chromosome transfer,[7] and BRCA2 by a candidate-gene approach.[8] FANCL was recently found through protein association studies.[9]

Most FA proteins assemble into a nuclear multiprotein ''core complex,'' which is required to catalyze a key reaction in the FA pathway: the activation of FANCD2 by monoubiquitination at position K561.[10] An important role for the assembly and/or stabilization of this complex has been assigned to FANCG, which belongs to the family of TPR-containing proteins.[11] FANCL, which carries a plant homology domain (PHD), is a candidate for acting as the ubiquitin E3 ligase in the monoubiquitination of FANCD2.[9,12] Monoubiquitination of FANCD2 is essential for the entire FA pathway because it allows FANCD2 to move into areas of damaged chromatin and to interact with BRCA1, resulting in repair of the damage.[10] BRCA2 and FANCJ are so far the only components of the pathway that act downstream (or independent) of the FANCD2 activation step.[4] The exact nature of the DNA damage response, which when defective causes FA, remains to be defined.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook


Post a comment