Understanding the mechanisms of DNA damage repair in the nucleosomal context
EMSL Project ID
51820
Abstract
Many human diseases, such as cancer, neuropathies, and others result from DNA damage. Estimates suggest that an average human cell sustains tens of thousands of lesions each per day. With ~10^13 cells in the body, it is unthinkable for a complex organism to survive without stringent DNA damage control and repair. One of the earliest elements of a double-strand break (DSB) DNA maintenance is a Sirtuin 6 (SIRT6) deacetylase. It was shown that SIRT6 actively deacetylates H3K56 at the DNA-break sites and is critical for the recruitment of an ISWI chromatin remodeler, SNF2h. The involvement of an ATP-remodeling and deacetylation indicates that chromatin structure modulation is critical for DNA damage response; if impaired recruitment of downstream repair factors (53BP1, RPA, BRCA1) is needed. In this project, we will investigate the recruitment of SNF2h to the nucleosome by SIRT6, visualize the interplay between individual subunits at high-resolution, and design experiments derived from the structural studies. We will also investigate a DNA-damage complex of ALC1 (CHD1-like protein) with PARP1 on the nucleosome, to compare different strategies the cells use to fix DNA lesions in the genome.
Project Details
Start Date
2021-02-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members