# Core 2: Structural Cell Biology (SCB) Core

> **NIH NIH P01** · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · 2020 · $461,429

## Abstract

Core 2 - Structural Cell Biology (SCB) Core
PROJECT SUMMARY/ABSTRACT
A major challenge for cancer structural biology in SBDR4 is to structurally define the DNA repair (DR) proteins
and assemblies that maintain genomic integrity. However. DR proteins and complexes have encoded flexibility
and function in spatially and temporally coordinated complexes that make their structural characterizations so
challenging. With SBDR investigators, Core B, the Structural Cell Biology (SCB) Core overcomes these
extreme challenges by combining macromolecular crystallography (MX) and small angle X-ray scattering
(SAXS) to structurally characterize almost every DR target. SAXS measures flexibility, conformations, and
assemblies, while MX provides atomic-level structural information. Together, SAXS and MX are synergistic and
complementary: they reveal the impact of sequence variations, the means to dissect multiple functions, and the
mechanisms whereby flexible and dynamic DR machinery functions. With the SCB Core based at the Berkeley
Advanced Light Source Synchrotron, the Core will uniquely provide SBDR laboratories unrivaled access 1) to
beamline facilities for MX and small angle X-ray scattering (SAXS) data collection, 2) to expertise of beamline
scientists, 3) to the latest developments in data analysis, and 4) to development of novel methods for their
Projects, as needed. SBDR members collect their own data or have data collected and analyzed for them. The
SCB Core will train and assist researchers, design and perform experiments. This will enable all Projects,
regardless of structural expertise, to optimally and efficiently address Project structural and mechanistic Aims
in ways that typical laboratories and beamline visits cannot or do not do. The impact of the SCB Core staff's
close collaborations and expertise in MX and SAXS are evident from their many publications with SBDR
members in all Projects. SCB Core-Project interactions will provide knowledge of DR structures,
conformations, and mechanisms as follows: Aim 1 is to provide SAXS measurement of flexibility,
conformations, and assemblies in solution, with added capabilities of high throughput SAXS and size exclusion
chromatography in-line with SAXS data collection. Aim 2 is provide atomic MX structures of components and
complexes, with added services for SAXS screening for crystallizability and with new MX hardware
developments. Aim 3 is to further develop hybrid methods for combining SAXS and MX, as well as observing
protein and DNA conformations using time-resolved SAXS. SCB Core collaborations address cross-Project
hypotheses that 1) DR proteins adopt specific conformational and/or assembly states to regulate binding,
activation and product release; 2) distinct functional conformations provide mechanisms to dissect, predict, and
control activities with small-molecules and mutations, and 3) controlling conformations, product release and
pathway handoffs provide the means to control synthetic lethalit...

## Key facts

- **NIH application ID:** 10003190
- **Project number:** 5P01CA092584-20
- **Recipient organization:** UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
- **Principal Investigator:** John A. Tainer
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $461,429
- **Award type:** 5
- **Project period:** 2001-09-27 → 2021-09-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003190

## Citation

> US National Institutes of Health, RePORTER application 10003190, Core 2: Structural Cell Biology (SCB) Core (5P01CA092584-20). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10003190. Licensed CC0.

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