EXAM 3 MOLECIULAR BIOLOGY DR. BORGON

The DnaA binds to the

Origin

`Initiation process involves

many proteon-protein interactions

DnaA helps

cut the DNA and help unwind it (melt DNA)

DnaB is considered to be a

Helicase

DnaC is considered to be a

helicase loader

Sliding clamps is loaded onto

the leading strand

Does the holoenzyme or DNA move?

Depending on the model; Replication Factory Model says that some helicases can form dimers and the Tradiitonal Model says that....

Trombone model is related to the

Phage

Eukaryotic...

MCM2-MCM7 forma dimer

E.coli prevents

Reinitiation

Palindrome define

Looks the same forwards and backwards

SeqA binds to

Hemimethylated DNA near oriC, blocking DnaA; aka it PREVENTS reinitiation

E. coli genome takes about

40 minutes

During E. coli replication,

Newly-replicated DNA is hemimethylted for a short time

what does hemimethylated DNA mean?

that one out of the two strands contains a methyl group (CH3)

Cell division takes about ______ hours long, with S phase being _____ hours long

24; 8

Origin licensing is in

G1

Origin firing in

S phase

The eukaryotic helicases

Are part of the pre-replication complex, recruit for genome replication, include negative supercoils

Eukarytoic helicases funation as a

Helicase, unwinds DNA,

Cyclins, CDKs and CDCs are involved in

Cell cycle timing; govern cell cycle

Some CDKs are low during G1 which means

You'll get helicase loading but not activation

CDK is low during ___ phase and high during ____ phase

G1; S

CD4 and CDK2 promote

G1 progression and S phase entry

Retinoblastoma (RB) is very important for

S phase progression

The end of the lagging strand is a

3' overhang

The lagging strand of the DNA is more difficult. At the end of the replication there is a gap which makes the DNA

Shorter, meaning as we age our chromosomes get SHORTER!

Telomerase is an

RNA/protein hybrid

Telomerase binds to the

Ends of our chromosomes

Telomerase synthesises in the

5' to 3' direction

Telomerase kepps on extending

The tips of our chromosomes

DNA requires an

RNA primer to start DNA synthesis

The RNA primers are removed by

Okazaki fragments and replaced by DNA

Telomeres have

10-15 kilobases of TTAGGG

Telomere length is regulated by

telomere-binding telomerase

What is true regarding the end replication problem?

To solve it, a primer terminal protein may be used instead of an RNA as the primer for the last Okazaki fragment.

why is there a 3' overhang in the lagging strand?

this is due to the inability to position the last Okazaki fragment at the end of the chromosome

People with shorter telomeres have

3x heart disease, 9x infectious disease death, worse cardiovascular surgery outcomes

What other animals have this same issue where the telomeres become shorter as you age?

Zebras and birds

What is the Hayflick Limit?

40-60 cell division for most cells before entering senescence; the point at which most cells become senescent as telomeres shorten

What disease has shorter telomeres?

Progeria, anemia, dyskeratosis congentia, lung fibrosis, liver scarring/cirrhosis, GI diseases, and others have shorter telomeres

Stress can also affect what?

Cellular aging, telomere length, and DNA repair

The telomeres are protecting us against

cancer

Senescence define

a process by which a cell ages and permanently stops dividing but does not die.

Asexual animals maintiain their

Telomere length somatically during replication

Asexual species are typically short-lives of sexual ancestors, so what's the advantage?

Allows the shuffling of new mutations and pathogen resistance

The human genome is ____ in length

2 meters

Genomes are wound around

Nucleosomes and condensed into chromosomes, which are found in the cell's nucleus

During mitosis chromosomes are found with

Two identical strands called sister chromatids

Chromatin is

Unraveled and accessible, and made up of both DNA and proteins

The overall architecture of the chromosome

Regulated gene expression

Viruses can be

ssRNA, dsRNA, or dsDNA

Bacterial genomes are typically

Circular (rarely linear) and millions of DNA base pairs long

Eukaryotic genomes are

Millions of base pairs long

Eukaryotes can be

haploid

What do polyploid cells do?

Allows for more RNA generation

Megakaryocytes for platelet production

Heart: 85% diploid and 15% tetraploid at 2, equal at 12, 27% diploid, 71% tetraploid, 2% octoploid in adults

Some dsDNA and dsRNA viruses have

Dense genomes and use both strands, with overlapping genes

The E. coli genome is composed almost entirely of

Genes, with a few transcriptional regulatory regions

The human genome is made up of _______ base pairs x _________ (1.5 gb of DNA/cell), `37 trillion cells in body

3 billion, 2 copies/cell

Only ______ grams of DNA in human body, but can stretch up to _______ miled

0.5 grams; 10 billion miles

Autosomes define

22 pairs, 1 copy from each parent

Sex chromosomes (X and Y) define:

Carry sex-determining genes. Evolved ~200-300 million years ago after split from monotremes, evolved independently in reptiles, birds, plants

Mitochondrial DNA define

Each cell has 500-2000 mitochondria, originating mostly from your mother. Circular, 16.5 kbp, 2-10 per mitochondrion, 500-10,000 copies per cell

Humans are _____% identical to other mammals the sequence level, but not organizationally

92%

Chimpanzees, bonobos, gorillas, orangutans have

24 chromosomes, MRCA with humans ~7-10 mya

Humans, Neanderthals, and Denisovans have

23 chromosomes, chromosome 2 is a fusion of homologs found in other primates, with vestigial centromere and telomeres

Humans and Neanderthals are ______% genetically identical,

99.84%

Modern humans carry _____% Neanderthal DNA, and ____% of Neanderthal genome is collectively in modern humans.

2-6%; 40%

We have ____ Neanderthal genes to fight RNA viruses that were transferred to us

152

1 in 3 European women carry a ___________ ________ from Neaderthals, with increased _________, fewer _________ during early pregnancy, and fewer ________.

Progesterone receptor; fertility; bleeding; miscarriages

Humans and Denisovans: people in Oceania have up to _____% Denisovan DNA

8%

DNA HOMOLOGY: Humans and chimps are _____% genetically identical (____% different), most divergence is in the ____ chromosome

98.77%; 1.2%; Y

Humans gained _____ genes and lost ____ genes after sploit, and have ____ new gene duplications

689; 86; 23

PROTEIN HOMOLOGY: ____% identical proteins, most differ by only two amino acids on average (_______ is identical)

29%; hemoglobin

What is the Ancestor's Tale

Some polymorphisms predate humans, and for certain genes you are more closely related to some chimpanzees than to some humans

Up to ___% difference in protein expression levels, variable by organ: 90% are up-regulated in _______ _______, but ______ and ________ have equal up and down regulation

40%: human brains; heart and liver

T/F: Chimps have more variation and higher mutation rate

true

What does FOXP2 in the brain control?

reading/writing, humans with defect have difficulties with both

FOXP2 differs in how many amino acids?

2 of 715 amino acids

ARGAP11B causes...

Bigger pool of brain stem cells, cerebellum expansion, folding of neocortex, found in Neaderthals, Denivosans, not chimps

DUF1220 is found in

Areas of the brain associated with higher cognitive function, 212 copies in humans, 37 in primates, 1 in mice.

Transgenic monkeys with human MCPH1 had better what?

Reaction times and short-term memory

MYH16 is...

Myosin variant in jaw muscles, found in all primates but humans

MYH16 (muscle) allowed for the evolution of

Smaller jaw muscles 2 million years ago which allowed the brian to grow larger

Loss of one type of keratin causes

Hair thinning

TASTE/DIGESTION: Humans have 3x more copies of ______, even variable among us.

Amylase

TASTE/DIGESTION: we also lost two bitter-tasting genes which are now ________

Pseudogenes

Both mutations of pseudogenes and amylase allow for

root/tuber digestion

HACNS1 is an

Enhancer

In HACNS1 there is how many nucleotide difference btween humans and chimps?

13

Most new beneficial mutations are ________, and are more likely on the ___ chromosmes, where are only a few immunity adaptations have occurred on autosomes

Recessive; X

Overlal the X chromosome is more/less variable at the sequence level between humans and chimps

Less

What happens when an X undergoes inactivation?

Soem women can develop disorders where hald of an organ's cells are mutant, but the inactivated X can still express up to 20% of its genes

What is the y chromosome that was once identical to the X doing?

It is the fastest evolving at the sequence level

____% of males carry the Genghis Khan's Y chromosome

0.5%

The Y chromosome has __________ _______ (___) homologous to the X chromosome, which recombine during _____

Pseudoautosomal regions (PAR); meiosis

There are 60 male specific genes that are often...

Repetitive and palindromic

What is SRY?

The male-specific transcription factor for sex determination

The Y chromosmes has been replaced in mice using only...

SRY and Eif2s3y (spermatogensis)

Majority of new mammalian genes are expressed in

testis