Multiscale Modeling of PCNA - Ubiquitin Interactions

Mechanism of CRL4, a PCNA-dependent E3 ubiquitin ligase

Eukaryotic cell cycle transitions are driven by E3 ubiquitin ligases that catalyze the ubiquitylation and destruction of specific protein targets. For example, the anaphasepromoting complex/cyclosome (APC/C) promotes the exit from mitosis via destruction of securin and mitotic cyclins, whereas CRL1 allows entry into S phase by targeting the destruction of the cyclin-dependent kinase (CDK) inhib...

SIVA1 directs the E3 ubiquitin ligase RAD18 for PCNA monoubiquitination

Translesion DNA synthesis (TLS) is a universal DNA damage tolerance mechanism conserved from yeast to mammals. A key event in the regulation of TLS is the monoubiquitination of proliferating cell nuclear antigen (PCNA). Extensive evidence indicates that the RAD6-RAD18 ubiquitin-conjugating/ligase complex specifically monoubiquitinates PCNA and regulates TLS repair. However, the mechanism by whi...

Multiscale modeling

Principles of Multiscale Modeling

Multiscale Modeling of Malaria

Parasitic infectious diseases like malaria and certain hereditary hematologic disorders are often associated with major changes in the shape and viscoelastic properties of red blood cells. Such changes can disrupt blood flow and, possibly, brain perfusion, as in the case of cerebral malaria. In recent work on stochastic multiscale models—in conjunction with large-scale parallel computing—we wer...