Editorial

Centrosome Structure and Function Under Normal andPathological Conditions

The centrosome is a nonmembrane-bound organelle of

about 1 lm in diameter (about the size of an E. coli cell).It is composed of a central pair of perpendicularly ori-

ented, nonidentical centrioles, surrounded by a diffuse

layer of protein scaffolding containing microtubule (MT)-

nucleating sites collectively known as the pericentriolar

material (PCM). Classical centrosomes are found in

nearly all animal cells. Although variations on the centro-

some are found in fungal and protozoal cells, they are not

present in plant cells.

Centrosomes are most often thought of in the context

of nucleating microtubules (MT) and organizing MT

arrays. As cellular organelles, they have been known for

well over a century, notably longer than the MT that they

organize. In animal cells, a single centrosome is found

next to the nucleus during most of interphase, while dur-

ing mitosis two centrosomes form the poles of the mitotic

spindle. In the guise of a basal body, centrosomal compo-

nents (notably the centriole) nucleate and promote growth

of cilia and flagella. Despite these noteworthy functions,

recent research has shown that this view of the role of

centrosomes is incomplete. For example, centrosomes

have been shown to be intimately involved in cytokinesis,

as well as in regulation of cell cycle progression. Further-

more, centrosomes have been shown to be key to the

unequal cell division that underlies stem cell replication

as well as differentiation. Even traditional, nominally

equal division has been shown to be asymmetric and

driven by the centrosome. These exciting new findings, as

well as research on the role of centrosomes in disease,

have prompted assembly and publication of this special

issue on the structure and physiology of the centrosome

under normal and pathological conditions.

The role of centrosomes in disease, especially cancer,

has been discussed and debated since the prescient publi-

cations of Boveri, and the article by Ried in this volume

provides a discussion of the often underappreciated detail

of Boveri’s observations and proposals, and a comparison

with current data on aneuploidy and cancer. Indeed, much

of this special issue addresses the involvement of centro-

somes in disease, and the findings presented by the

authors may have surprised even Boveri.

Centrosome replication is semiconservative, as is repli-

cation of the DNA that will be divided between daughter

cells under the organizing influence of the centrosome.

The article by Lukasiewicz and Lingle presents a review

of the structure and replication cycle of the centrosome.

The mitotic role of centrosomes in apportioning equal

copies of DNA to two daughter cells has contributed to a

focus on the role of the centrosome in symmetric division.

However, as already noted, it has now become clear that

centrosomes also play a critical role in asymmetric or

unequal division during differentiation and in stem cells.

These findings have recently led to a reassessment of the

equality of ‘‘normal’’ division. The role of centrosomes

in processes that may require unequal division, including

problems that this asymmetric process may pose for

endeavors such as nuclear transfer stem cell technology,

is discussed in the article by Schatten and Sun.

Many of the protein components that comprise the cen-

trosome have recently been identified using proteomic

methods, and the roles played by many of these proteins

have also been recently investigated and described. The

role of the Aurora A kinase, whose expression is often

modified in cancer, is described in the article by Lukasie-

wicz and Lingle. BRCA1, a protein whose activity is

changed in some cancers, is also involved in centrosome

function via interaction with g-tubulin, and this is the

focus of the article by Parvin. Description of the role of

Mps1 in centrosome defects is provided in the article by

Kasbek et al., and Moore and Golden describe the evi-

dence supporting the notion that some centrosomal pro-

teins are dual-function proteins that also have mitochon-

drial localization and function.

Centrosome function has been found to be compro-

mised in a number of pathophysiologic conditions. The

results of this dysfunction are not always evident, but

they can include effects on centrosome replication control,

Received 20 August 2009; provisionally accepted 22 August 2009; and

in final form 24 August 2009

DOI 10.1002/em.20535

Published online 22 September 2009 in Wiley InterScience (www.interscience.

wiley.com).

VVC 2009Wiley-Liss, Inc.

Environmental andMolecular Mutagenesis 50:591^592 (2009)

microtubule organizing activity, and reproductive success.

The path between compromised centrosome replication

control and genomic instability is discussed by Kasbek

et al. in the context of the role of Mps1, a protein kinase

required for centrosome duplication. The accumulation of

compromised centrosomes during aging of porcine

oocytes, and accompanying effects on reproduction are

discussed in the article by Miao et al.

An altered centrosome replication cycle, or altered link-

age to the DNA replication cycles, can lead to an excess

number of centrosomes with variable functioning

capacity. The presence of multiple centrosomes, and the

role of that excess in diseases such as cancer, has been

discussed since the time of Boveri. In normal animal

cells, the number of centrosomes is tightly regulated,

though the number is not always two. Clearly, the mere

presence of more than two centrosomes will not inevita-

bly lead to a diseased state, because some normal cells

have many more than two. For example, megakaryocytes,

the progenitor cells of platelets, have many, apparently

fully functional centrosomes, and this condition is normal.

However, centrosome amplification is often associated

with aneuploidy and cancer, and several papers address

recent findings on this subject. The article by Difilippan-

tonio et al. addresses the fact that many supernumerary

centrosomes are lacking structural features that correlate

with loss of microtubule nucleation capacity. The occur-

rence of aneuploidy and centrosome excess in myeloma is

reviewed by Chng and Fonseca.

The origin of aneuploidy in spontaneous cancers is of-

ten not clear; however, experimental induction can open a

window into the process. A trio of papers in this issue

present research on chemical and physical induction of

aneuploidy and centrosome amplification. From the chem-

ical side, Yu et al. show that exposure of cultured cells to

antiretroviral nucleosides can induce centrosome amplifi-

cation. Physical agents can lead to similar outcomes. Mor-

rison et al. demonstrate that DNA damage from ionizing

radiation can induce centrosome amplification, and they

examine the role of centriole separation in the phenom-

enon. Sargent et al. show that carbon nanotubes can

induce aneuploidy, and the phenomenon may result from

physical interference with the mitotic spindle.

In a final section of this issue, the ability of viruses to

induce aneuploidy is reviewed. The contribution by Jeang

et al. reviews the general subject of viral transformation

with a focus on aneuploidy induction, while Duensing

et al. focus on the human papillomavirus oncoproteins

and their role in viral-induced centrosome amplification.

It is clear that many exciting new developments have

led to an increased appreciation of the complexity of the

centrosome and the nuanced role that it plays, not only in

cell division, but also in interphase. The awareness of the

inherent inequality of the two centrosomes has led to an

appreciation of the role of the centrosomes in generating

unequal division in stem cells and differentiating cells.

Moreover, although the pioneering studies of Boveri were

published over a century ago, the role of excess centro-

somes in disease, especially cancer, continues to be the

focus of intense research. This special issue provides the

reader with an effective overview of recent developments

in centrosome research. We sincerely believe that Boveri

would be pleased, and hope that it will stimulate research

interest and catalyze new developments.

ACKNOWLEDGMENTS

We wish to thank all of the authors and the reviewers

for their efforts. In addition, we wish to thank the senior

editorial staff Paul White, Iain Lambert, and Carole Yauk,

as well as the EMM adminstrators Christine Lemieux and

Alexandra Long, for supporting us in the development

and production of this issue. This work was supported in

part by the Intramural research funds of the Eunice Ken-

nedy Shriver National Institute of Child Health and

Human Development and of the National Cancer Institute.

Dan L. SackettLaboratory of Integrative and Medical BiophysicsProgram in Physical BiologyEunice Kennedy Shriver National Institute of ChildHealth and Human Development

Bethesda, Maryland

Ofelia OliveroLaboratory of Cancer Biology and GeneticsNational Cancer InstituteNational Institutes of HealthBethesda, Maryland

Environmental and Molecular Mutagenesis. DOI 10.1002/em

592 Editorial