Maternal age-dependent APC/C-mediated decrease in securin causes premature sister chromatid separation in meiosis II

Abstract Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.

Twinning in Susceptible Mothers—An Exploratory Study of International Data by Payami's Models Suggests “Reproductive Maturity” as a Risk Factor

Acta geneticae medicae et gemellologiae twin research ◽

10.1017/s0001566000003469 ◽

1991 ◽

Vol 40 (3-4) ◽

pp. 269-289 ◽

Cited By ~ 1

Author(s):

P. Philippe

Keyword(s):

Maternal Age ◽

Comparison Group ◽

Linear Increase ◽

Reproductive Maturity ◽

Secondary Exposure ◽

Twin Birth ◽

Age Dependent ◽

Common Etiology ◽

International Data ◽

The Common

AbstractAn attempt has been made to apply Payami's models to maternal age-specific twin birth prevalences in several countries. The models disclose the heterogeneity of a cohort and spell out the risks to susceptible members (who will actually get the disease) according to age (or time). Payami's method specifies that the typical cohort of susceptibles is ascribed to two exposures: a potent and generalised exposure and a very low or no risk secondary exposure. The models have been adjusted to international data from current as well as old populations, of Occidental and Japanese origin. Results show that cohorts of twin-prone mothers aged 25 to 45 are homogeneous. A single dominant etiology is suggested which applies to both MZ and DZ twins. Heterogeneity, from 10% to 25%, is present in all countries whenever the 20-24 age group is involved. A separate study of illegitimate twin births from Denmark reduces the heterogeneity and shows that MZ illegitimate twin births are due to a secondary exposure responsible for a distinct twinning etiology. The age-specific risks of a MZ illegitimate twin birth are much higher than those of any comparison group, and are constant until age 35 years. This suggests a single-hit exposure akin to a neuroendocrine stimulus which short-cuts the usual age-dependent etiologic pathway. MZ and DZ twins both experience the same maternal age specific risks, an observation which underscores the common etiology of both types of twins. Risks increase with age from age 20 to 45 years. The pattern according to age varies among countries and time periods. Occidental populations have a pattern varying from an exponential to a more linear increase in old and recent populations, respectively. Only present-day Japan displays a logarithmic-like growth curve. The concept of “reproductive maturity” is introduced, and related to the secular trend of the DZ twin birth risk and to its variation across countries. Two new conclusions are drawn: a) The higher the rate of reproductive maturity, the less the DZ twin birth risk and, b) Reproductive maturity determines the maternal age-specific gonadotropin levels.

Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase

Nature ◽

10.1038/nature02256 ◽

2003 ◽

Vol 427 (6972) ◽

pp. 364-370 ◽

Cited By ~ 222

Author(s):

Gregory C. Rogers ◽

Stephen L. Rogers ◽

Tamara A. Schwimmer ◽

Stephanie C. Ems-McClung ◽

Claire E. Walczak ◽

...

Keyword(s):

Sister Chromatid ◽

Sister Chromatid Separation