# DNA processing roles in DNA Double-strand Break repair by Fanconi Anemia sub-complex AG20

> **NIH NIH F31** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $44,045

## Abstract

Project Summary
 The Fanconi Anemia (FA) pathway forms a complex DNA repair network that can mediate tumor
aggressiveness and therapy-resistance when dysregulated in cancers. Although FA proteins have been shown
to support cancer survival, the poor characterization of FA pathway biochemical activities that contribute to this
phenotype has made therapeutic targeting of these proteins very challenging. Characterization of novel
enzymatic roles carried out by FA components could serve as valuable clues into how certain FA proteins are
able to promote cancer radiotherapy resistance and would provide identifiable targets for sensitization of
cancer cells to traditional treatments. Specifically, FA proteins FANCA, FANCG, and FAAP20, which form a
sub-complex (AG20), and FANCA-interacting protein BRCA1 may provide critical care of the unstable cancer
genome through FANCA’s intrinsic DNA/RNA binding and newly discovered strand annealing/exchange
activities. These activities could contribute to DNA double-strand break repair, which is capable of conferring
survival advantages to radiotherapy-treated cancer cells. The goal of this proposal is to further determine
additional DNA and RNA processing activities of BRCA1 and the AG20 sub-complex, and how these activities
are utilized in a cellular context to preserve the genome. The aims of this project are: 1) identify biochemical
activities of BRCA1 and the AG20 sub-complex related to nucleic acid processing events: defining the range of
activities AG20 and FANCA/BRCA1 are able to perform using DNA/RNA substrates will be possible using
highly active recombinant protein that our lab is well-equipped to generate; 2) determine the chromatin
landscape that facilitates FANCA/BRCA1 and AG20-mediated repair: FANCA’s cellular role in DSBs across
different chromatin contexts can be analyzed in fine detail through ChIP-Seq analysis of U2OS-DiVA cells
present in our lab, and live cell imaging of FANCA recruitment to site-specific DNA damage. By accomplishing
these goals, we expect to be able to delineate a working model for the participation of repair factors BRCA1
and AG20 in subsets of DNA damage repair that supports cancer survival and therapy-resistance.

## Key facts

- **NIH application ID:** 10066409
- **Project number:** 1F31HL151097-01A1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Anna Louise Palovcak
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $44,045
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066409

## Citation

> US National Institutes of Health, RePORTER application 10066409, DNA processing roles in DNA Double-strand Break repair by Fanconi Anemia sub-complex AG20 (1F31HL151097-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066409. Licensed CC0.

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