DNA-Protein Interactions

Table of Contents

Overview

DNA-protein interactions are fundamental to life processes, governing genome replication, repair, recombination, and transcriptional regulation. This resource systematically organizes major protein families that interact with DNA, providing a framework for understanding their coordinated roles in cellular functions.

Classification Framework

This resource employs a Structure-Enzyme-Regulation framework that organizes DNA-binding proteins by their primary molecular roles:

I. Structural Proteins

Establish and maintain the physical architecture of DNA/chromatin.

DNA packaging proteins Histones (H2A, H2B, H3, H4), Linker histone H1

3D genome organization Cohesin (loop formation), CTCF (boundary factor), Condensin (mitotic condensation), SMC5/6 (genome stability)

Nuclear architecture Lamin A/C, Nuclear matrix proteins (SAF-A)

Architectural modulators High-Mobility Group (HMG) proteins, DNA bending factors

II. Enzymatic Proteins

Catalyze chemical reactions on DNA.

DNA replication enzymes DNA polymerases (α, δ, ε), MCM complex (helicase), Primase

DNA repair enzymes DNA Ligase (I, III, IV), PARP1, Nucleases (XPF, FEN1), Rad50

DNA recombination enzymes RecA/Rad51/Dmc1 (homologous recombination)

DNA topoisomerases Topoisomerase I, Topoisomerase II (relieve supercoiling)

DNA modification enzymes DNA methyltransferases (DNMT1/3A/3B), TET enzymes (demethylation)

DNA helicases RecQ family (BLM, WRN), UvrD, Pif1

III. Regulatory Proteins

Modulate gene expression without forming stable structures.

Transcription factors p53 (tumor suppressor), MYC (growth regulator), NF-κB (inflammation master), Nuclear receptors (ER, GR)

Chromatin remodelers SWI/SNF (BAF complex), INO80, ISWI, CHD family (ATP-dependent remodeling)

Histone modifying enzymes HATs (p300/CBP, GCN5), HDACs (Class I/II/III/IV), HMTs (EZH2, SUV39H1), HDMs (LSD1, JMJD2)

Epigenetic readers BRD4 (acetyl-lysine reader), HP1α/β/γ (methyl-lysine reader), CBX proteins (Polycomb readers)

Transcriptional co-regulators Mediator complex (MED1/12/14), p300/CBP (co-activators), NCoR/SMRT (co-repressors)

Classification Frameworks

Zheng Z, Wang Y (2011) Biomol Concepts 2011 Aug 1;2(4):293-303. DNA binding proteins: outline of functional classification
Luscombe NM et al. (2000) Genome Biology 1:reviews001. An overview of the structures of protein-DNA complexes

Last Updated: 2025-11-24
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