DNA Repair Protein Interactions

**9**

**Chapter 2**

**Abstract**

Interactions

*Nina Moor and Olga Lavrik*

environment, and the step of BER process.

**1. Introduction**

Coordination of DNA Base

Excision Repair by Protein-Protein

The system of base excision repair (BER) evolved to correct the most abundant DNA damages in mammalian cells is the most essential for maintaining the genome integrity. The multistep BER process involves several enzymes and protein factors functioning in a coordinated fashion that ensures the repair efficiency. The coordination is facilitated by the formation of protein complexes stabilized via either direct or indirect DNA-mediated interactions. This review focuses on direct interactions of proteins participating in BER with each other and with noncanonical factors found recently to modulate the efficiency of BER. All the known partners of main BER participants, the sites responsible for their interaction, and the characteristics of protein-protein affinity are summarized. Well-documented evidences of how DNA intermediates and posttranslational modifications of proteins modulate protein-protein interactions are presented. The available data allow to suggest that the multiprotein complexes are assembled with the involvement of a scaffold protein XRCC1 and poly(ADP-ribose) polymerase 1, a key regulator of the BER process, irrespective of the DNA damage; the composition and the structure of the complexes are dynamically changed depending on the DNA damage, its chromatin

**Keywords:** base excision repair, protein-protein interactions, noncanonical factors,

Many forms of DNA damage are generated due to permanent action of endogenous and exogenous factors. In order to maintain genome integrity, cells have evolved several specific pathways to repair DNA lesions. Base excision repair (BER), which ensures correction of the most abundant damages—modified nitrogenous bases and apurinic/apyrimidinic (AP) sites—is critically important for survival of human cells [1–3]. Enzyme and protein factors of BER also participate in the repair of DNA single-strand breaks (SSBs) considered as a separate pathway of the BER system [4, 5]. The other repair systems (**Figure 1**) deal with bulky nucleobase lesions (NER), DNA double-strand breaks (HR; NHEJ), and mismatched bases (MMR). Impaired DNA repair is associated with embryonic lethality, rapid aging, and a variety of severe human hereditary diseases as well as development of cancer [7, 8]. The balance of DNA damage and DNA repair is highly relevant to both

posttranslational modifications of proteins, coordination of DNA repair
