BIS2A Final

Proofreading by DNA Polymerase

Occurs during REPLICATION fixing 99% of the errors

Mismatch repair (MMR)

the correction of mistakes that escape the DNA polymerase proofreading activity (occurs AFTER replication)

Direct Chemical Reversal

No excision of DNA backbone (energy efficient!)

Base Excision Repair (BER)

-Glycosylase detects and removes damaged base

-generates an AP site

-Endonuclease cuts site

-DNA polymerase and ligase repair break

Nucleotide Excision Repair (NER)

-~20-30 bases (larger than BER)

-fixes damage down by a Thymine Dimer

-Thymine dimer: a photolesion produced by UV radiation in sunlight

Transcription occurs in the

5' to 3' direction

Protein Phosphorylation

-REVERSIBLE modification

-Reversed by PHOSPHATASES

-can either activate/inactivate the proten

-involves protein kinases

Regulatory Proteins

control the activity of other proteins

e.g. kinases and phosphatases

Translation control

Eukaryotic initiation factor-2 (eIF-2)

-first protein to bind to the mRNA that helps initiate translation

Protein glycosylation

-permanent modification

-addition of sugar moieties to proteins

Ubiquitination: Targeted protein degradation

-reversible modification

-protein degraded by proteasome

-target proteins tagged with ubiquitin by special enzymes

Epigenetics

The study of heritable phenotype changes that do not involve alterations in the DNA sequence

DNA Methylation

-DNA methyltransferase

-takes place at C sites of CG sequence

-maintained after replication

-functions as heritable information

-represses gene expression at promoters

Histone modifications

1. Histone methylation: Gene repression or activation

2. Histone acetylation: Gene activation

Interphase

all non-mitosis phases (S, G1, G2)

1 Nucleosome

8 units of histone

Condensins

ATP dependent proteins that further help condense the chromatin

S phase

DNA replication

Mitosis consists of

prophase, prometaphase, metaphase, anaphase, telophase

Prophase

prepare the poles where the chromosomes will move

Prometaphase

Attach one copy of each chromosome to each pole

Metaphase

Chromosomes are lined up at the metaphase plate

Telophase

Move the chromosomes to the poles and divide the cells

Cohesin

-protein that holds sister chromatids together

-cleaved in anaphase after chromosomes are correctly attached to the mitotic spindle

G1 phase

Gap phase for growth for replication

G2 phase

Gap phase for division

G1 checkpoint

-Is cell division necessary?

=Is the cell large enough?

Tumor suppressr genes

RB, P53

Cyclins and CDKs

-Cyclin (only made at a certain point in the cell cycle) binds to Cdk exposing its active site

-Protein subtrate and ATP bind to Cdk, substrate is phosphorylated

-Phosphorylated protein regulates cell cycle

When is cyclin synthesized?

G1 phase

Retinoblastoma (RB) protein

blocks entry into S phase

What happens to RB when CDK is activated?

CDK phosphorylates RB, RB is now inactive --> start of S phase

DNA damage checkpoint

Cell cycle checkpoint to recognize DNA damage

Cell cycle checkpoint

Coordinates cell cycle in undamaged normal cells

Double-strand break (DSB) repair

1. Homologous recombination (HR)

2. Non-homologous end joining (NHEJ)

Homologous recombination (HR)

-Error free: template based from sister chromatid

-Predominant repair in germ cell, to maintain integrity of genome

Non-homologous end joining (NHEJ)

-Error prone: random repair

-Predominant repair in somatic cells

HR in mitotic cells

Maintenance of genome integrity

HR in meiotic cells

Contributes to genetic diversity