Ubiquitination of proliferating cell nuclear antigen (PCNA) in response to DNA damage leads to the recruitment of specialized translesion polymerases to the damage locus. This constitutes the initial step in translesion synthesis (TLS) � a critical pathway for cell survival and for maintenance of genome integrity. To address the issue of conformational flexibility and determine the structure of Ub-PCNA in solution, we combined multi-scale computational modeling and small angle X-ray scattering (SAXS). This combined strategy revealed alternative positions for ubiquitin to reside on the surface of the PCNA homotrimer, distinct from the position identified in the recent crystal structure by M. T. Washington et al. These computationally-derived positions, in an ensemble with the crystallographic and flexible positions, provided the best fit to the solution-phase scattering, indicating that ubiquitin is dynamically associated with PCNA and capable of transitioning between a few preferred sites on the PCNA surface.

Solution phase X-ray scattering and multiscale computational modeling reveal the structural dynamics of ubiqutinated PCNA

243rd National Meeting (2012)

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