BRIT1/MCPH1: a guardian of genome and an enemy of tumors.
The DNA of every cell is constantly exposed to insult mediated by endogenous and environmental factors that induced damage in its structure. To react to these attacks and maintain the integrity of the genome, eukaryotic cells are equipped with sophisticated mechanisms to detect, signal the presence of and repair DNA damage. The cellular response to DNA damage is a critical event for maintaining genomic stability and limiting neoplastic transformation. BRIT1, a newly identified protein, forms specific irradiation-induced nuclear foci. Our recent investigation demonstrates that BRIT1 functions as a proximal factor in the DNA damage checkpoints that control multiple damage sensors and early mediators. BRIT1 is also implicated in cell cycle checkpoints, controlling and regulating other important molecules and thus affecting the timing of mitosis. Depletion of BRIT1 abolishes the DNA damage response and results in centrosomal abnormalities and chromosomal aberrations. Moreover, aberrantly reduced expression of BRIT1 in human carcinomas implicates this protein in cancer initiation and progression. Together, the findings identify BRIT1 as a potential tumor suppressor. Fully elucidating the function of this intriguing protein may lead to new therapeutic approaches for the improved cancer treatment.
Chaplet
Michael
M
Department of Molecular Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
Rai
Rekha
R
Jackson-Bernitsas
Deborah
D
Li
Kaiyi
K
Lin
Shiaw-Yih
SY
D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D003598:Cytoskeletal Proteins; D004249:DNA Damage; D016678:Genome; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1