Most of the neural cells are derived from neural progenitor cells (NPCs) lining the ventricles of human brain. NPCs follow two major particular patterns in their division including symmetric and asymmetric cell divisions (Brand and Rakic 1979) . The first pattern results in two identical NPCs which are switched on to the latter type of division at specific time of brain development to generate one NPCs and one post mitotic neuron. It was found that every deviation at the proper time of switch between these two types of neural cells divisions can affect the number of neuron pools. It was also assumed that deregulations in asymmetric and symmetric cell divisions lead to micro- and macro-cephaly, respectively (Doe and Bowerman 2001) . Functional studies on the orthologous of MCPH1 gene in Drosophila have shown that it may have pivotal role in control of asymmetric cell division and also determining the right time of switching from symmetric to asymmetric cell divisions. Moreover, the important role of MCPH1 gene in regulation of centrosome activity which itself plays crucial role in mitosis of neurons, would be a further evidence of determining activity of MCPH1 in brain development (Yamashita et al. 2003) . As mentioned above, centrosome governs two major cell cycle checkpoints before and after getting entry into the G2. There is an intra S checkpoint in which DNA synthesis is prohibited when the cell is exposed to radiation. This task is mediated by activation of ATM which induces CHK1 to stall the replication process through inactivation of Cdck25A and subsequently Cdk2-cyclin complex (Fig. 7.3) (Abraham 2001; Margolis and Kornbluth 2004) . In this way, co working of MCPH1 seems to be necessary for the proper activity of the major cellular proteins including ATM and BRCA1 which guarantee the G2/M checkpoint to be intact. Cdc27 and Cdc16 which are the elements of anaphase promoting complex (APC) has been shown to be phosphorylated with C-terminal BRCT domains of MCPH1 to drive the separation of chromosome during mitosis. MCPH1 can alternatively binds to another component of APC complex called Cdc26 when the Cdc27 has been mutated. Cdc26 differs from Cdc27 at the residue residing on + 1 amino acid relative to phosphoserine (Singh et al. 2012) . These interactions of MCPH1 are necessary for APC complex stability and may shed light on this finding that loss of MCPH1 can mimics the loss of APC complex function.

Determination of MCPH1 expression in seckel syndrome patients with severe microcephaly revealed that normal level of MCPH1 transcription is required for active centrosome Chk1 expression and eventually induction of centrosome cyclin B-Cdk1 (Tibelius et al. 2009) . It was demonstrated that directed mutagenesis of MCPH1 gene was associated with arrest of manipulated cells in G2 phase and premature condensation of chromosomes (Alderton et al. 2006) . Moreover, directed mutagenesis of MCPH1 led to decrease in tyrosine phosphorylation of Cdk1 in S and G2 phases and consequently formation of PCC in manipulated cells. It also was associated with the aberrant G2-M checkpoint and nuclear fragmentation when DNA has been damaged (Alderton et al. 2006). It is obvious that MCPH1 has a major contribution in controlling the main cellular checkpoints throughout the cell cycle.

Presence of BRCT domains within the structure of MCPH1 protein would be a good predictor of its role in DNA repair system like other proteins carrying two carboxyl- terminal BRCT domains (PTCB). BRCT domain actually provides the suitable context for peptide and phosphopeptide binding activities (Rodriguez et al. 2008; Manke et al. 2003) . Localization of MCPH1 in the DNA damage site and DNA repair complex could be a convincing evidence of its contribution in DNA repair pathway (Fig. 7.4) (Rai et al. 2006; Alderton et al. 2006; Lin et al. 2005) . Loss of MCPH1 prevents activation of other DNA damage proteins including Rad51, BRCA2 and Chk1/Chk2 dependent pathways (Tibelius et al. 2009) . It was shown that biallelic knock out of MCPH1 gene in mice was associated with decreased length of life and genomic stability (Trimborn et al. 2010; Liang et al. 2010) . It was described that the C-terminal domains of MCPH1 protein play pivotal role in DNA repair process (Yu et al. 2003) . It is in line with the capability of N-terminus defective MCPH1 protein to avoid promotion of damaged cell to get entry in to the mitosis (Gavvovidis et al. 2010) . Study on the role of MCPH1 aberrations in endometrial cancer have revealed that deletion of one nucleotide within the repeated tracts of adenine in exons 4, 5 and 8 was compatible with mismatch repair (MMR) deficiency and microsatellite instability (MSI). It was proposed that this type of deletion is associated with non-functional C-terminal domains. The same inefficient MCPH1 protein had been reported prior that wherein deletion of 38 bps within the exon 10 was found in breast cancer (BC) (Alderton et al. 2006). Of note, there is a similar A tract in exon 10 of ATR gene as the major cooperators of MCPH1 in DSB that any monoalleleic alteration of it was reflected by poor prognosis of endometrial cancer patients carrying MSI (Xu et al. 2004). It could be extrapolated that haplo-sufficiency of major components of DSB system is essential for maintaining the stability of genome and prevention of tumor progression in particular in endometrial cancer.

The better response to chemo- and radio-therapy in patients harboring mutations in genes encoding DSB repair components could be a strong reason to seek the harmful mutations within them especially in MCPH1 gene (Li et al. 2004; Rodriguez et al. 2008) .