**6. References**

154 DNA Repair

Fig. 4. Schematic representation of Rad51 interactions with its direct partners involved in its posttranslational modification and the steps of HR (top). Localization of binding sites in the

In all living organisms HR is strictly regulated in time and in space to maintain the stability of the genome. Rad51 is the central protein in the HR process. The regulation of HR involves many protein interactions (Fig. 4) which are strongly dependent on posttranslational modifications. Indeed, almost all key mediator proteins of HR are subject to phosphorylation by specific kinases, thereby modulating some stage of this process (e.g. the nucleofilament formation). Hence, these posttranslational reactions underline the complexity of the regulation of HR. Despite of the several studies on the mechanism of

The impact of phosphorylation on the interactions of Rad51 with its partners still needs to be determined. In order to better understand the regulation of HR, the future challenge will

This work was supported by grants from the Ligue contre le Cancer Comité de Loire Atlantique et du Morbihan. SH is supported by a fellowship from the Region Pays de la Loire (CIMATH2 grant). MP was supported by a fellowship from Conseil Général des Pays

Rad51 phosphorylation, its biochemical role in the HR reaction remains unclear.

be to identify the complete interaction network of Rad51, the motor protein of HR.

hRad51 sequence (bottom).

**5. Acknowledgment** 

de Loire-Atlantique (Atlanthèse grant).

**4. Conclusion** 


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**10** 

*Canada* 

**Post-Transcriptional Regulation of E2F** 

**and Survival in Development & Disease** 

Cells are continually exposed to genotoxic stresses. Upon DNA damage, the cell activates a coordinated and complex series of responses (Levitt and Hickson, 2002). Multiple factors are implicated in each of these responses. Recently, it has become apparent that various transcription factors play important roles in cellular responses to genotoxic stress. In particular, E2F transcription factors are key for the activation of genes involved in these

E2F family comprises two subfamilies, termed E2F and DP, and includes orthologs expressed across many species, from plants to higher vertebrates (McClellan and Slack, 2007). In mammals, multiple E2F (E2F-1 through -8) and DP (DP-1 through -4) genes have been identified. E2F-1, -2 and -3 are associated with DNA synthesis and cell cycle progression, and function as heterodimers with a DP member (McClellan and Slack, 2007). E2F-4 and -5 also require association with a DP protein, but often function to halt cell cycle progression associated with terminal differentiation or reversible entry into quiescence (McClellan and Slack, 2007). E2F-1 through -5 can mediate transcriptional activation when found as "free" E2F/DP dimers, but can also act as transcriptional repressors if they are associated with a member of the retinoblastoma (pRb) family of proteins (Hallstrom and Nevins, 2009). In contrast, E2F-6 lacks both transcriptional activation and pRb-binding domains, and functions as a constitutive transcriptional repressor. The most divergent members of the E2F family are E2F-7 and -8, which bind neither DP nor pRb-family proteins, and also function as transcriptional repressors to mediate cell cycle arrest (Lammens et al., 2009). To regulate gene expression, E2F factors bind GC-rich elements on proximal promoters, which can conform to either a consensus 5'-TTTC[CG]CGC-3' element, or to non-consensus sequences (Judah et al., 2010; Rabinovich et al., 2008). Considerable efforts have been directed to investigate whether different E2F proteins exhibit target selectivity. Genome-wide screens for E2F targets have revealed considerable overlap in the ability of individual E2F proteins to regulate their targets, although a few promoters activated by specific E2F forms have been identified

**1. Introduction** 

processes.

(Cao et al., 2011).

**Transcription Factors: Fine-Tuning** 

**DNA Repair, Cell Cycle Progression** 

Lina Dagnino, Randeep Kaur Singh and David Judah

*University of Western Ontario* 

