| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000433590 |
| 005 | | 20200225144131 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781088388716 |
| 035 | |
▼a (MiAaPQ)AAI22618250 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 574 |
| 100 | 1 |
▼a Allard, Corey A.H. |
| 245 | 10 |
▼a Molecular Mechanisms of Cell Size Control in Fission Yeast. |
| 260 | |
▼a [S.l.]:
▼b Dartmouth College.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 249 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-05, Section: B. |
| 500 | |
▼a Advisor: Moseley, James B. |
| 502 | 1 |
▼a Thesis (Ph.D.)--Dartmouth College, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a Control of cell size requires coordination between growth and division, which is achieved through molecular size sensors that are coupled to the cell cycle. In eukaryotes, progression through the cell cycle is controlled by regulated activity of the protein kinase cyclin-dependent kinase 1 (Cdk1), which phosphorylates and activates many substrate proteins that function in mitosis and subsequent cell division. Cdk1 activity is regulated by signal transduction cascades that carry information about cell size, but how cell size information is encoded within these signal transduction networks is largely unknown. In fission yeast cells, cell growth and division are balanced such that cells divide at a highly reproducible size. Previous studies demonstrated that proper control of cell size at division requires Wee1 kinase, which phosphorylates and inhibits Cdk1 specifically in small cells, which prevents cells from dividing at too small a size. The molecular mechanism by which Wee1 inhibits Cdk1 specifically in small cells is poorly understood. Previous studies implicated Cdr2 kinase, which oligomerizes to form membrane-associated "nodes" at the medial cell cortex. I investigated how Cdr2 nodes inhibit Wee1 during cell growth using biochemical and fluorescence microscopy approaches. I show that Wee1 localizes to nodes in short bursts that require Cdr2 kinase activity. These bursts increase in frequency and duration as cells grow. Size dependent signaling is due in part to the Cdr2 inhibitor Pom1 kinase. Pom1 phosphorylates and inhibits Cdr2 and forms cortical concentration gradients from cell poles. Pom1 inhibits Cdr2 nodes specifically in small cells, but the time and place of their regulatory interactions were unclear. I show that Pom1 forms stable oligomeric clusters that dynamically sample the cell cortex. Binding frequency is patterned into a concentration gradient by the polarity landmarks Tea1 and Tea4. Pom1 clusters colocalize with Cdr2 nodes, forming an inhibitory threshold against node activation. The shape of the Pom1 concentration gradient changes if cells are starved of glucose, resulting in disruption of Cdr2 signaling. My work reveals how Pom1-Cdr2-Wee1 operates in multiprotein clusters at the cortex to promote mitotic entry at a cell size that can be modified by nutrient availability. |
| 590 | |
▼a School code: 0059. |
| 650 | 4 |
▼a Cellular biology. |
| 650 | 4 |
▼a Biology. |
| 650 | 4 |
▼a Molecular biology. |
| 690 | |
▼a 0379 |
| 690 | |
▼a 0306 |
| 690 | |
▼a 0307 |
| 710 | 20 |
▼a Dartmouth College.
▼b Molecular and Cellular Biology. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-05B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0059 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15493524
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |