High impact information on clk-2

• We propose that atl-1 and rad-5/clk-2 respond to single-stranded DNA generated by replication stress and function with atm-1 following DSB resection [1].
• Here, we show that atl-1 (Caenorhabditis elegans ATR) and rad-5/clk-2 prevent mitotic catastrophe, function in the S-phase checkpoint and also cooperate with atm-1 in the checkpoint response to DSBs after ionizing radiation (IR) to induce cell cycle arrest or apoptosis via the cep-1(p53)/egl-1 pathway [1].
• ATL-1 is recruited to stalled replication forks by RPA-1 and functions upstream of rad-5/clk-2 in the S-phase checkpoint [1].
• In C. elegans, clk-2 mutants have elongated telomeres, and clk-2 overexpression can lead to telomere shortening [2].
• We discuss how the phenotype of clk-2 mutants could be the result of altered patterns of gene expression [2].

Biological context of clk-2

• Here, we show that clk-2 encodes a regulator of telomere length in C. elegans [3].
• Embryonic development strictly requires the activity of maternal clk-2 during a narrow time window between oocyte maturation and the two- to four-cell embryonic stage [2].
• Strikingly, abrogation of the clk-2 checkpoint gene rescued lethality and developmental defects, and eliminated cell-cycle arrest and apoptosis after dUTPase depletion [4].

Other interactions of clk-2

• A different mechanism is specified by the clock genes clk-1, clk-2, clk-3 and gro-1, which regulate metabolic activity and the pace of many temporal processes including longevity [5].
• We show that rad-5/clk-2 acts in a pathway that partially overlaps with the conserved C. elegans mrt-2/S. cerevisiae RAD17/S. pombe rad1(+) checkpoint pathway [6].

References