# Homolog bi-orientation and segregation in oocyte acentrosomal meiosis

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $385,656

## Abstract

During the first meiotic division, homologous chromosomes linked by chiasmata attach
to microtubules from opposite poles of the spindle (bi-orient) and then segregate. Our long term
goal is, using Drosophila melanogaster females as a model, to understand the mechanisms that
promote accurate chromosome segregation on the acentrosomal spindle of oocytes. In humans,
errors in chromosome segregation in the oocyte lead to aneuploidy and are the leading cause of
miscarriage, infertility and birth defects. Thus, we are particularly interested in the protein
complexes and mechanisms of bi-orientation and the features of the oocyte spindle that makes it
susceptible to chromosome segregation errors. In the absence of the microtubule-organizing
center found at mitotic spindle poles, the chromosomes generate a signal which stimulates
spindle assembly.
 In the previous funding period, we genetically defined how two types of microtubule
attachment are used for bi-orientation: first lateral attachments establish bi-orientation, then end-
on attachments are required for maintenance and segregation. We found that the chromosome
passenger complex (CPC) is required for both the formation of a bipolar spindle and kinetochore
assembly in oocytes. The CPC localizes to the centromeres and the central spindle, which is
composed of overlapping antiparallel microtubules adjacent to the chromosomes. Based on
these results, the premise of the proposed studies is that bi-orientation depends on lateral
interactions between the kinetochores and centrals spindle microtubules. We will test the
hypothesis that SPC105R recruits additional proteins for meiosis-specific functions by
determining which domains function in lateral attachments and co-orientation and identifying
proteins that interact with SPC105R. To investigate the function of CPC at centromeres and
central spindle during meiosis I, mutants to target the INCENP to the central spindle and
centromeres will be studied. We will also test the hypothesis that bi-orientation is established by
lateral attachments between kinetochores and central spindle microtubules. We will examine
kinetochore-microtubule attachments in central spindle mutants, determining whether lateral
and/or stable end-on attachments are formed.
 The Aims of this proposal are linked by a goal to understand the mechanisms of
chromosome segregation that are unique to the oocyte. Upon completion of this work, we will
have identified important components that have meiosis specific functions at the kinetochores,
determined the role of the central spindle in bi-orientation, and characterized how this is
regulated by the CPC. We will have gained insight into the mechanisms that promote bi-
orientation in oocytes via the CPC, kinetochores, and central spindle. Because they are
acentrosomal, there are probably segregation mechanisms that are unique to oocytes. It is
important to understand these mechanisms that may make the oocyte acentrosomal spindle
susceptible ...

## Key facts

- **NIH application ID:** 9955263
- **Project number:** 5R01GM101955-08
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** KIM S MCKIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,656
- **Award type:** 5
- **Project period:** 2013-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955263

## Citation

> US National Institutes of Health, RePORTER application 9955263, Homolog bi-orientation and segregation in oocyte acentrosomal meiosis (5R01GM101955-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9955263. Licensed CC0.

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