Structure and Function of DNA Repair Proteins: Lesion Recognition

Accurate DNA repair and replication are critical for genomic stability and cancer prevention. RAD51 and its gene family are key regulators of DNA fidelity through diverse roles in double-strand break repair, replication stress, and meiosis. RAD51 is an ATPase that forms a nucleoprotein filament on single-stranded DNA. RAD51 has the function of finding and invading homologous DNA sequences to enable accurate and timely DNA repair. Its paralogs, which arose from ancient gene duplications of RAD51, have evolved to regulate and promote RAD51 function. Underscoring its importance, misregulation of RAD51, and its paralogs, is associated with diseases such as cancer and Fanconi anemia. In this review, we focus on the mammalian RAD51 structure and function and highlight the use of model systems to enable mechanistic understanding of RAD51 cellular roles. We also discuss how misregulation of the RAD51 gene family members contributes to disease and consider new approaches to pharmacologically inhibit RAD51.

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Quantitatively profiling acetylome of DNA repair proteins in early DNA damage

10.21203/rs.3.rs-44043/v1 ◽

2020 ◽

Author(s):

Shiqin Li ◽

Lin Zhou ◽

Xinli Liu ◽

Bingbing Shi ◽

Tingting Huang ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Protein Function ◽

Critical Role ◽

Repair Process ◽

Post Translational Modification ◽

Affinity Enrichment ◽

Dna Repair Proteins ◽

Liquid Chromatography Tandem Mass ◽

And Function

Abstract Background：Lysine acetylation is a reversible regulated post-translational modification that can regulate the stability, localization, and function of proteins in multiple cellular processes. However, the regulative mechanism of acetylation on the repair proteins in the early DNA damage is not fully understood. Methods：We performed a global proteome and acetylome of DNA repair proteins in DNA damage in 1 h after treated with epirubicin by using high affinity enrichment and high-resolution liquid chromatography–tandem mass spectrometry approaches. Results: 190 Kac sites in 50 repair proteins were identified in cells treated with epirubicin as compared to the control. 42 acetylated lysine sites and 24 deacetylated lysine sites were observed in 21 and 16 repair proteins, respectively. 7 repair proteins simultaneously contained both acetylated and deacetylated lysine sites. 11 acetylation sites were located in the function domains of 7 repair proteins that might reveal mechanisms by which acetylations alter DDR protein function. In 17 repair proteins, the induced acetylation changes were for the first time identified in the present study. Conclusion: The proteome and acetylome results indicated that fast acetylation or deacetylation on these repair proteins might play a critical role in the early DNA damage repair process.

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