THE BIOCHEMICAL REGULATION OF CHROMOSOME FORMATION AND

SEGREGATION IN MITOSIS/MEIOSIS

By: GOSIFE DONALD OKOYEGENETICS 301

APRIL 13TH 2015

● Definition of Important Concepts○ Eukaryotic Chromosome○ Chromatin○ Chromatid

● Formation of the Eukaryotic Chromosome○ Biochemistry and regulation of nucleosome

formation○ Nucleosome packing (heterochromatin vs

euchromatin)○ Chromosome condensation

● Chromosomes during Mitosis and Meiosis○ Biochemical regulation of Mitosis and Meiosis

OVERVIEW

● EUKARYOTIC CHROMOSOMES: Structures resulting from the organization of nuclear DNA.

● CHROMATIN: A complex of macromolecules consisting of DNA, proteins and RNA. Basically resulting from packaging of DNA with histone proteins.

● CHROMATID: One copy of a duplicated chromosome usually joined to another via a centromere.

IMPORTANT CONCEPTS

NUCLEOSOMES: Histone proteins with DNA wrapped around them● DNA: Negatively charged● Histones: Positively charged

o Core (H2A, H2B, H3, H4)o Linker Histone (H1)

NUCLEOSOME FORMATION

● H3-H4 dimers assemble● DNA associates● H2A/H2B associate with

tetramer● Histone Octamer forms● H1 for higher order

packing

ASSEMBLY

● Individual Core Histone Proteins Aggregate unspecificallyo Random coil conformation in low ionic conditions

● Interacting Core Histones adopt similar and more stable secondary conformations fostering further interactions

● Interactions with DNA are also favoredThe resulting interactions produce modifiable tails.● Histone Chaperones

STABILITY OF HISTONE PROTEINS

● Binds Entry/Exit site of DNA to nucleosome

● Stabilizes Nucleosome

● Reduces nucleosomal mobility

● Guides higher order folding

● Accumulates in transcriptionally inactive regions

● Closely linked to DNA modification

H1 LINKER HISTONE

● Histone Acetyltransferases (HATs)

o Lysine Residues

● Histone Deacetylases (HDACs)

● Histone Methyltransferases (MTs)

o Lysine or Arginine residues

● Histone Demethylases (DMTs)

● Condensin: I and II

OTHER PROTEINS THAT REGULATE NUCLEOSOME PACKAGING

Chromatin Remodeling Complexes (CRC): ● establish a proper chromatin context for central

nuclear processes such as replication, DNA repair, and gene expression.

● move or evict nucleosomes to allow access to DNA for regulatory proteins that otherwise would be impeded by their binding to the nucleosomal DNA

● the mode of nucleosome movement and rearrangement is the topic of epic scientific debates

HIGHER ORDER PACKING

● Folding continues guided by CRC and other proteins.

● The microenvironments determine the rate of folding and the concentration of linker histones

● The folding pattern closely mimics the double-helix nature of DNA but in a much tighter form.

HIGHER ORDER PACKING continued...

REGULATION OF CHROMOSOMAL ACTIVITIES DURING MITOSIS/MEIOSIS

● PROPHASE: Chromosome Condense

● METAPHASE: Chromatids attach to mitotic spindle

equator

● ANAPHASE: Sister Chromatids separate and migrate

● TELOPHASE: Chromosome uncoils

MITOSIS AND THE CHROMOSOME

● Occurs during metaphase

● Determines if mitosis will

continue

MITOTIC CHECKPOINT

● Cohesin● BUB1 (Budding Uninhibited by

Benzimidazole-1)● MAD1/MAD2/MAD3● cdc20 (Cell Division Cycle 20)● Anaphase-Promoting Complex● Securin-Separase Complex● Cyclin-Dependent Kinase-1● BUBR1 (Budding Uninhibited by

Benzimidazole Related-1)

THE METAPHASE-ANAPHASE TRANSITION IS HIGHLY REGULATED

● cdc 20● cdc14 (Cell Division Cycle 14)

(phosphatase)● APC● Securin-Separase Complex● Separase● Cohesin

This represents the last regulated step of mitosis

THE METAPHASE -ANAPHASE TRANSITION IS HIGHLY REGULATED

● Very similar to mitosis

● Meiotic Crossover

o Regulation of number and distribution by DPY-

28

o A subunit of condensin

REGULATION OF CHROMOSOMES IN MEIOSIS

The Eukaryotic Cell is:● A master biochemist

● A master strategist........a grand chessmaster

IN SUMMARY

● "Chromatin Structures" by Original uploader was Richard Wheeler at en.wikipedia Later version(s) were uploaded by Seans Potato Business at en.wikipedia. - Transferred from en.wikipedia; Transfer was stated to be made by User:sevela.p.. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Chromatin_Structures.png#/media/File:Chromatin_Structures.png

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