Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

Article Abstract:

An analysis of a panel of human lung hyperplasias is done, which shows that all of them retain wild-type p53 genes and had no signs of gross chromosomal instability and also found signs of a DNA damage response. It is proposed that cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.

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Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks

Article Abstract:

The structure of the domain of the protein 53BP1 that recruits it to sites of double-strand breaks (DSBs) is solved. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues.

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Resistance to therapy caused by intragenic deletion in BRCA2

Article Abstract:

The significance of the intragenic deletion of a BRCA2 mutation in the development of resistance against the poly(ADP-ribose) polymerase (PARP) is analyzed. Cells with loss of the BRCA2 function are found to be highly sensitive to the PARP inhibitors.

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