namely TIN2, rather than on POT1. Alto-
gether, these results converge to a model
where TPP1 in vivo, similarly to the in vitro
findings, binds to telomeres and connects
them to telomerase, and this activity may
evolve different shelterin subcomplex re-
Other proteins binding to the single-
stranded region of telomeres also may
be involved in modulation of telomerase
activity. For instance, an additional OB-
fold-containing protein, related to an
RPA large subunit, was found to be asso-
ciated with a highly processive form of
telomerase in the ciliate Tetrahymena
thermophila (Min and Collins, 2009). Simi-
larly, a novel protein factor, CTC1, was
described recently at telomeres (Miyake
et al., 2009; Surovtseva et al., 2009).
found in plants and humans shares
sequence similarities with Cdc13 and
possesses functions in telomere protec-
tion. However, it remains to be examined
whether it is also involved in telomerase-
dependent telomere length homeostasis.
The question to answer now is how
TPP1 coordinates both end protection
and telomerase recruitment, and how
this duality is eventually regulated as
a function of telomere length in normal
somatic cells. Likewise, how is this
balance eventually altered in cancer
cells? Indeed, if TPP1-POT1 is required
for protection, are all telomeres bound to
it? Do TPP1-containing complexes invari-
ably serve both roles at all bound telo-
meres? Future experiments in the field
will certainly shed new lights on this
aspect of the increasingly complex and
dynamic world of chromosome ends.
Abreu, E., Aritonovska, E., Reichenbach, P.,
Cristofari, G., Culp, B., Terns, R.M., Lingner, J.,
and Terns, M.P. (2010). Mol. Cell. Biol., in press.
Published online April 19, 2010. 10.1128/MCB.
Evans, S.K., and Lundblad, V. (1999). Science 286,
Latrick, C.M., and Cech, T.R. (2010). EMBO J. 29,
Min, B., and Collins, K. (2009). Mol. Cell 36,
Shimamura, S., Tamura, M., Yonehara, S., Saito,
M., and Ishikawa, F. (2009). Mol. Cell 36, 193–206.
Y.,Nakamura, M.,Nabetani, A.,
Sabourin, M., and Zakian, V.A. (2008). Trends Cell
Biol. 18, 337–346.
Surovtseva, Y.V., Churikov, D., Boltz, K.A., Song,
M., Price, C.M., and Shippen, D.E. (2009). Mol. Cell
Tejera, A.M., Stagno d’Alcontres, M., Thanasoula,
M., Mario, R.M., Martinez, P., Liao, C., Flores,
J.M., Tarsounas, M., and Blasco, M. (2010). Dev.
Cell 18, this issue, 775–789.
Wang, F., Podell, E.R., Zaug, A.J., Yang, Y., Baciu,
P., Cech, T.R., and Lei, M. (2007). Nature 445,
Xin, H., Liu, D., Wan, M., Safari, A., Kim, H., Sun,
W., O’Connor, M.S., and Songyang, Z. (2007).
Nature 445, 559–562.
A Deathly DNase Activity for Dicer
Katsutomo Okamura1and Eric C. Lai1,*
1Sloan-Kettering Institute, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10065, USA
Recently reporting in Science, Nakagawa et al. describe an unexpected role for Dicer in chromosome frag-
mentation during apoptosis in C. elegans. They find that cleavage of DCR-1 by the caspase CED-3 redirects
its regulatory activity, by destroying its dsRNase activity while activating an intrinsic DNase activity.
RNase III enzymes are a widely distrib-
uted family of double stranded RNA
the discovery of E. coli RNase III in the
1960s, the functions of this protein family
in ribosomal RNA biogenesis and mRNA
decay or regulation have been well
studied in bacteria and yeast (MacRae
and Doudna, 2007). Importance of their
recognized only in the last decade. In
particular, Dicer-family RNase IIIenzymes
are central to the biogenesis of Argo-
naute-associated small regulatory RNAs,
including microRNAs (miRNAs) and small
miRNAs play important roles in diverse
essential for many aspects of develop-
ment and physiology. The cell death
pathway has critical connections with
the miRNA pathway, since many indi-
vidual miRNAs have proapoptotic or anti-
apoptotic activities. Deregulation of such
miRNAs may contribute to various human
cancers (Garzon et al., 2009).
mentation, which can be visualized by
TUNEL (terminal deoxynucleotidyl trans-
ferase-mediated dUTP nick end labeling)
staining. In mammals, the endonuclease
DFF40 (also known as CAD) initiates DNA
2005). The DNase activity of DFF40 is nor-
mally inhibited by DFF45 (also known as
ICAD), but when the cysteine protease
caspase-3 is activated, it cleaves DFF45
to release active DFF40. Despite strong
conservation of the cell death pathway in
C. elegans, including the functional cas-
pase-3 ortholog CED-3 (Miura et al.,
1993; Yuan et al., 1993), its genome does
not appear to encode homologs of DFF40
and DFF45. Nevertheless, as apoptotic
cells in C. elegans exhibit DNA fragmenta-
nucleaseactivity is apparently responsible
for initiating this process in nematodes.
Developmental Cell 18, May 18, 2010 ª2010 Elsevier Inc.