Current proteomics methods applicable to dissecting the DNA damage response

Monita Muralidharan; Nevan J Krogan; Mehdi Bouhaddou; Minkyu Kim

doi:10.1093/narcan/zcad020

Current proteomics methods applicable to dissecting the DNA damage response

NAR Cancer. 2023 May 19;5(2):zcad020. doi: 10.1093/narcan/zcad020. eCollection 2023 Jun.

Authors

Monita Muralidharan^{1

2}, Nevan J Krogan^{1

2}, Mehdi Bouhaddou^{1

2

3

4}, Minkyu Kim^{1

2

5}

Affiliations

¹ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
² Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA 94158, USA.
³ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90024, USA.
⁴ Quantitative and Computational Biosciences Institute (QCBio), University of California, Los Angeles, CA 90024, USA.
⁵ Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA.

Abstract

The DNA damage response (DDR) entails reorganization of proteins and protein complexes involved in DNA repair. The coordinated regulation of these proteomic changes maintains genome stability. Traditionally, regulators and mediators of DDR have been investigated individually. However, recent advances in mass spectrometry (MS)-based proteomics enable us to globally quantify changes in protein abundance, post-translational modifications (PTMs), protein localization, and protein-protein interactions (PPIs) in cells. Furthermore, structural proteomics approaches, such as crosslinking MS (XL-MS), hydrogen/deuterium exchange MS (H/DX-MS), Native MS (nMS), provide large structural information of proteins and protein complexes, complementary to the data collected from conventional methods, and promote integrated structural modeling. In this review, we will overview the current cutting-edge functional and structural proteomics techniques that are being actively utilized and developed to help interrogate proteomic changes that regulate the DDR.

Abstract

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