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An integrative structural study of the human full-length RAD52 at 2.2 A resolution.

ABSTRACT: Human RAD52 (RAD52) is a DNA-binding protein involved in many DNA repair mechanisms and genomic stability maintenance. In the last few years, this protein was discovered to be a promising novel pharmacological target for anticancer strategies. Although the interest in RAD52 has exponentially grown in the previous decade, most information about its structure and mechanism still needs to be elucidated. Here, we report the 2.2 Å resolution cryo-EM reconstruction of the full-length RAD52 (FL-RAD52) protein. This allows us to describe the hydration shell of the N-terminal region of FL-RAD52, which is structured in an undecamer ring. Water molecules coordinate with protein residues to promote stabilization inside and among the protomers and within the inner DNA binding cleft to drive protein-DNA recognition. Additionally, through a multidisciplinary approach involving SEC-SAXS and computational methods, we comprehensively describe the highly flexible and dynamic organization of the C-terminal portion of FL-RAD52. This work discloses unprecedented structural details on the FL-RAD52, which will be critical for characterizing its mechanism of action and inhibitor development, particularly in the context of novel approaches to synthetic lethality and anticancer drug discovery.

SUBMITTER: Balboni B

PROVIDER: S-EPMC11306251 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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An integrative structural study of the human full-length RAD52 at 2.2 Å resolution.

Balboni Beatrice B Marotta Roberto R Rinaldi Francesco F Milordini Giulia G Varignani Giulia G Girotto Stefania S Cavalli Andrea A

Communications biology 20240808 1

Human RAD52 (RAD52) is a DNA-binding protein involved in many DNA repair mechanisms and genomic stability maintenance. In the last few years, this protein was discovered to be a promising novel pharmacological target for anticancer strategies. Although the interest in RAD52 has exponentially grown in the previous decade, most information about its structure and mechanism still needs to be elucidated. Here, we report the 2.2 Å resolution cryo-EM reconstruction of the full-length RAD52 (FL-RAD52) ...[more]

PMID: 39112549

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Dataset Information

An integrative structural study of the human full-length RAD52 at 2.2 A resolution.

Publications

An integrative structural study of the human full-length RAD52 at 2.2 Å resolution.

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