In my end is my beginning: control of end resection and DSBR pathway 'choice' by cyclin-dependent kinases.

The genome is constantly subjected to chemical alterations that have the potential to cause genetic mutation, chromosomal rearrangements and, in the case of multicellular organisms, cancer. Particular vulnerability exists during DNA replication, when the two DNA strands of a chromosome separate to form templates for the synthesis of sister chromatids. Attempted replication across a damaged or nicked DNA template can result in the formation of a double-strand break (DSB), arguably the most dangerous of DNA lesions. DSBs can also arise directly at any cell cycle stage following exposure to ionizing radiation or radiomimetic agents. To combat these recurrent threats of genomic instability, numerous distinct enzyme systems have evolved that sense DNA damage and coordinate its repair. Part of this coordination involves the activation of signal transduction cascades that target repair proteins, trigger DNA damage-dependent cell cycle checkpoints and profoundly affect chromatin neighboring a DSB. Here, we discuss current models of how lesion processing itself helps to coordinate these signals in dividing cells. Recent evidence in yeast of a role for cyclin-dependent kinases in DNA end resection suggests a possible solution to the long-standing puzzle of how DSBR pathway 'choice' is regulated through the cell cycle.