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Hypothetical Model on the Functions of the WRN, BLM and MRE11

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Hypothetical Model on the Functions of the WRN, BLM and MRE11

• WRN and BLM are genes encoding DNA helicases mutated in the human progeria syndromes: Werner and Bloom Syndromes. MRE11 complex is mutated in genetic instability syndromes: Nijmegen breakage syndrome and ataxia telangiectasia-like disorder. All three may be involved in the resolution of a stalled replication fork and in checkpoint signaling during S phase. DNA replication fork stalling results in the formation of abnormal structures and occurs at frequencies sufficient to be a significant source of endogenous DNA damage. BLM may be recruited to these sites resulting in its phosphorylation by ataxia telangiectasia mutated protein-related protein (ATR). The activated or phosphorylated BLM determines the proper recruitment of the MRE11 complex. WRN may be required at this point to provide endonuclease or helicase activity. Also at this stage, WRN may be phosphorylated by ATR or by MRE11 and NBS1, resulting in checkpoint reinforcement. Replication recovery can also involve homologous recombination (HR) and BRCA1 and RAD51.

Adapted from Franchitto A. et al, Human Molecular Genetics 11:2447, 2002.

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mRNP Transport through the Nuclear Pore Complex (NPC)

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Cargo Import by the Importin-Importin Pathway

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Modular Structure of Transcription Factors

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Transcription Activation by Nuclear Receptors [1 of 2]

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Transcription Activation by Nuclear Receptors [2 of 2]

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Coupled RNA Splicing and Nuclear Export

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RNA Polyadenylation

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Mammalian mRNA Polyadenylation Machinery

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RNA Maturation

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RNA-guided Epigenetic Control of Gene Expression

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Phosphorylation-driven Regulatory Switchfrom Transcription Initiation to Elongation