Distinct mobility patterns of BRCA2 molecules at DNA damage sites

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bioRxiv. 2023 Feb 20;. doi: 10.1101/2023.02.20.527475

Paul Maarten, Aaron Jesse, Wait Eric, van Genderen Romano, Smal Ihor, Chew Teng-Leong, Kanaar Roland, Wyman Claire

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Abstract

BRCA2 is an essential tumor suppressor protein involved in promoting faithful repair of DNA lesions. The activity of BRCA2 needs to be tuned precisely to be active when and where it is needed. Here, we quantified the spatio-temporal dynamics of BRCA2 in living cells using aberration-corrected multifocal microscopy (acMFM). Using multicolor imaging to identify DNA damage sites, we were able to quantify its dynamic motion patterns in the nucleus and at DNA damage sites. While a large fraction of BRCA2 molecules localized near DNA damage sites appear immobile, an additional fraction of molecules exhibit restricted motion, providing a potential mechanism to retain an increased number of molecules at DNA lesions. Super-resolution microscopy revealed inhomogeneous localization of BRCA2 relative to other DNA repair factors at sites of DNA damage. This suggests the presence of multiple subcompartments at the chromatin surrounding the DNA lesion, which may play an important role in the contribution of BRCA2 to the regulation of the repair process.

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bioRxiv PrePrint https://doi.org/10.1101/2023.02.20.527475

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Distinct mobility patterns of BRCA2 molecules at DNA damage sites

Abstract

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