**3. Structural & functional integrity is essential for protein interactions with partner molecules**

The efficient performance of DNA repair processes requires the coordinated actions of many players and mainly depends on proper interactions between the protein components of each pathway involved which in turn mainly relies on their functional structure (structure – function relationship). At least three major mechanisms influence protein function due to or independently of its tertiary structure:


Scheme 2. Simplified Scheme of major steps of DNA Double strand break repair by Homologous Recombination.

The efficient performance of DNA repair processes requires the coordinated actions of many players and mainly depends on proper interactions between the protein components of each pathway involved which in turn mainly relies on their functional structure (structure – function relationship). At least three major mechanisms influence protein function due to or

a. Missense mutations in the coding region can modify the primary structure of a protein resulting in dys-functional folding of the protein, and / or instability in the cellular

b. Post-translational modifications (phosphorylation, ubiquitination, ribosylation and acetylation) regulating distinct interactions with partner molecules driving the various

c. Regulation of the protein levels, availability through regulation of the quantity of the protein, which can drive cell decisions in improper pathways, leading to abnormal cell cycle progression, cell division and possibly malignant transformation or aggressive

Scheme 2. Simplified Scheme of major steps of DNA Double strand break repair by

pathways in which the protein in question is implicated.

**3. Structural & functional integrity is essential for protein interactions with** 

**partner molecules** 

environment.

tumor progression.

Homologous Recombination.

independently of its tertiary structure:

The fundamental proteins involved in the HRR pathways are highly conserved in almost all organisms ranging from bacteria to human. The significance of this repair system is also indicated by the fact that defects in HRR cause human hereditary cancers as well as sporadic tumors. In many cases the dysfunction of proteins observed in many tumors helps to elucidate all three categories of the mechanisms mentioned above and to clarify different aspects of DDR pathways (Murphy & Moynahan, 2010).

Herein we will focus on current information regarding the structure – function relationship of two key players in regulation and performance of DSB repair – the most deleterious reported lesion of the genome – BRCA1 and RAD51. BRCA1 is a core component of many multi-molecular complexes involved in DNA damage detection, HR regulation, cell cycle regulation and genome transcription. RAD51, a key factor of HRR, replaces RPA on the produced single strands of damaged DNA and performs the search for homologous DNA strand and exchange in order to restore the damaged DNA sequence according to its sister chromatid. Moreover, RAD51 is implicated in telomere maintenance via ALT pathway and is also involved in mitochondrial DNA repair. Via at least its indirect interaction with BRCA1 as well as with direct p53 complex formation, RAD51 seems to be an interplayer responsible for communication between DNA repair effectiveness, cell replication, apoptosis or senescence decisions.
