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SFM Quiz 2 > Functions/Dysfunctions of Genomic Regulation > Flashcards

Functions/Dysfunctions of Genomic Regulation Flashcards

1
Q

central dogma

A

dna-rna-protein

reverse transcriptase turns rna to dna

only mrna becomes protein

retroviruses can turn rna to DNA

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2
Q

DNA composition

A

deoxynucleotitde with PO sugar, missing OH and base

represented in 5’-3’ direction

the 3OH end is connected to a phosphodiester linkage to the 5’ phosphate of the next nucleotide

every DNA strand has a phosphate residue at the 5’ terminus and a free OH at the 3’

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3
Q

the two DNA strands are aligned

A

antiparallel, form the right handed B form via hydrophobic bases in the interior and hydrophilic sugar backbones in the exterior

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4
Q

base pairing

A

AT with two H bonds

GC with three H bonds

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5
Q

Eukaryotic Packaging

A

DNA double helix wraps around pairs of four histones

this forms the nucleoside

H1 histone is attached to linker DNA

nucleosides are further packaged into 30nm fibers and then to chromatin

when cells divide in the M phase, chromatin condenses into chromosomes

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6
Q

mitotic chromosomes are condensed 500 times when compared with interphase chromosomes. Why?

A

to prevent physical damage to the DNA as chromosomes are spearated and passed on to daughter cells

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7
Q

142 H bonds between DNA and the histone octamer in each nucleosome as well as

A

hydrophobic interactions and salt linkages

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8
Q

histone proteins are highly conserved across species

A

only 2 AA different between pea and cow H4

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9
Q

proteins that bind DNA are made of two classes

A

histone proteins
non histone chromosomal proteins ‘

each nucleosome core particle consists of a complex of 8 HP, histone octamer which DNA winds around.

Protein +DNA is chromatin

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10
Q

only ___ of proitein coding sequence in DNA

A

1.5%

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11
Q

Euchromatin

A

loosely packed, easily accesible, transcriptionally active found in nondividing cells

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12
Q

heterchromatin

A

tightly packed, dense, inaccesibly, transcriptionally inactive

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13
Q

posttranslation modifications happen on

A

histone tails.

the core histone H2A and H2B can also be modified

combinations of moidifcations constitute the histone core

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14
Q

methyltion/demethylation

A

transger 1-3 methyl groups from S-adenosyl-L-methionne to lysine or arginine residues of hostone by histone methyltransferase (HMT)

HMTs control DNA methylation through chromatin transcriptional dependent repressino/activation

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15
Q

acetylation

A

enzymatic addition of an acetyl group from acetyl CoA

involvedin the regulation of many processes, gene silencing, cell cycle, apoptosis

uses aceyltransferases (HATs) which acetylate H3 and H4

H3 acetylation can be increased by unhibition of histone deacetylases and decreased by HAT inhibition

imbalance in acetylation has been assocaited with cancer

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16
Q

deacetylation

A

represses genes by compacting the chromatin, uses HDACs

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17
Q

Phosphorylation

A

associated with local chromatin opening and transcriptional acitvation

linked with chromatin condensation during mitosis

important for regulation of DNA damage repsonse

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18
Q

semiconservative DNA replication

A

each parental strand of DNA is the template for the daughter

each replicated molecule contains one parent strand and one new strand

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19
Q

bidirectional DNA replication

A

replication of DNA in a eukaryotic chromosome (goes in both directions)

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20
Q

semidiscontinuous DNa replication

A

both new DNA strands are synthesized in teh 5-3 direction.

leading strand is made continuously wherase lagging strand is made with Okazaki framgents

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21
Q

DNA polymerase

A

needs a primer to start synthesis

adds in the 5-3 direction
uses free nucleotide triphoshate as substrates

the free 3OH group of the primer attacks the P of the incoming NTP therby releasing the terminal two PP and hydrolysis of the PP drives the reaction

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22
Q

DNA helicase

A

melts H bonds and unwinds DNA

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23
Q

topoisomerase

A

releives coil strain ahead of replication fork

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24
Q

ssDNA binding protein

A

keeps template strands separated

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25
Q

topoisomerase inhibitors as anticancer drugs

A

block cell cycle, generate single and double stranded breaks, harms the genome, leads to apoptosis and death

ex: Type I irinotecan, folfori, etopsiside, anthracyclines

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26
Q

DNA ligase

A

seals nicks

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27
Q

Nucleoside analog inhibtors

A

DNa synthesis involves the formation of 3-5 phosphodiester bonds

because of that, nucleoside analogues lack the 3OH group and act as drugs to inhibit DNA repliction

these nucleosides need to be converted to dNTPs before they can act as inhibitors of DNA polymerase

ex. acyclovir, others

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28
Q

both acyclovir and AZT lack 3OH thus

A

arresting viral DNA synthesis by acting as chain terminators

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29
Q

spontaneous damage by endogenous agents

A

deprivation of adenosine and guanosine via removal of their bases, purination occurs via hydrolysis of N glyucosyl linkage giving rise to abasic/apurininc sites in the DNA strand

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30
Q

deaminiation of the bases A, G and C make

A

hypoxanthine, xantine, uracil

31
Q

ionizing radiation

A

xrays, results in ROS and cause base famage, break strands, cross link DNA protein

32
Q

nonionizing radiation

A

UV light damages DNa by indicating the formation of covalent linkages between adjacent pyrimidine bases, forming thymine dimers and 6-4 linkages

33
Q

depurination

A

5000 purine lost/bases per day

example guanine gets hydrolyzed off and only sugar P left

34
Q

deamination

A

C to U changes, 100 bases per day. In DNA this is bad for replciation

left with a sugar phpshate

35
Q

AGT can be deaminated and adenine will turn into hypoxanthine which increases

A

uric acid and gout

36
Q

Outcomes of DNA damage

A

unrepared DNA damage can lead to deleterious consequences such as impaired cellular function, programmed cell death and mutations that lead to cancer

37
Q

polymerase proofreading

A

double checks the bases match?

38
Q

direct repair

A

enzymatic

repairs pyrimidine dimers

39
Q

6 methylguanine

A

uses DNA photolyase, methylgianine methyltransferase

40
Q

base excision repair

A

repairs single BASE mismatches, nondistoring alterations like depurination

involves DNA glycolysis, AP endonuclease, AP lyas, DNA polymerase, DNA ligase

41
Q

nucleotide excision repair

A

repairs chemical changes that distort DNA like pyrimidine dimers, BPDE-guanine adductor, cisplatin adducs

involves NER protein complex, DNA polymerase E, DNA ligase

disease Xeroderma Pigmentosum

42
Q

mismatch repair

A

repairs mismatched base in daughter strand

involves MER complex, helicase, endonuclease, DNA polymerase D, DNA ligase,

dz is hereditary nonpolyposis, colorectal cacners

43
Q

recombination: nonhomologous end joining

A

repairs double strand breaks, interstrand cross linking

involves damaged ends that are filled in and joined

some base pairs may be mising

mulitple proteins and enzymes including DNA ligase

44
Q

recombination: homologous recombination

A

repairs double strand breaks, interstrand cross linking

involves ligases, DNA polyermase, MER system

damaged duplex repair using infmration on undamage homologous duplex

dz is BRCA 1-2

45
Q

transcription coupled repair

A

repairs stalled RNA polymerase during transcription (not replication)

dz is cockayne

46
Q

translation synthesis

A

bypases synthesis

repairs unprepared thymine dimers

involves DNA polymerase (reduced fidelity polymerases)

47
Q

Xeroderma Pigmentsum

A

skin sensitivity to direct sunlight

prone to melanomas

causes cyclobutane dimers to form in the DNA

can be repaired through NER but that is defective in the XP proteins (A-G) in the NER complex in those with the dz

48
Q

Cockayne Syndrome

A

rare, autosomal recessive congenital disorder

mutant genes invovled are ERCC6 and 8

these genes code for their proteins and are invovled in the TCR of DNA

if DNA not repaired, cell death occurs

sx include neuro isses, photosensitivity, progeria

mutations in ERCC8 and 6 lead to cockayne A and B respectively with B being more common `

49
Q

BRCA 1 and 2

A

tumor suppresor genes

increase risk for breast cancer 5x the norm
as well as ovarian cancer before meno

men with these mutations have increased resik for breast cancer as well

BRCA1 increases cervical cacner, iterine, pancreatic colon in women and pancreatic, testicular, prostate in men

men more oftenaffected by BRCA2 with increase risk for melanoma, pancreas, stomach, gallbladder and bile duct for women

50
Q

imprinting

A

certain genes from mother or father are expressed while other s are silenced

impriented allele are silenced such that the gene is expreseed only from the non-imprinted parent

epigenetic process that invovles the methylation and histone modification of egg and sperm during formation while genetic seuqence is unchanged

duplicated in all somatic cells

prader willi

51
Q

epigenetics

A

mechanism for regualting gene acticity indepdent of DNA sequence that determines which genes are turned off or on in a specific cell in different disease states

can be develeoped in childhood, utero, drugs, diet, lifestyle

52
Q

More on Methylation

A

methyl group from diet can tag DNA and activate or repress gnes

added to A or C by methyltrasnferase

changes activity of promoter

does not change sequence

repress gene transcription when at the gene promotor

essential for normal development

assocaited with normal development, impriinting, x inactivation, aging, tetc

53
Q

More on histone acetylation/deacetylation

A

HATs acetylate core histones to neutralize positive charge on lysine and help chromatin decondsnse

acetylate nonhistones as well like TF

inhibtors of HAT show promise in dz tx.

HDACs remove acetyl groups from lysine on core histones and non histone proteins

cancer cells are very sensitive to inhibitors of lysine deacetylases like vampiric acid (anticancer, anti sz)

54
Q

CpG islands

A

adjacent C-phosphate-G assocaited with inactive genes

55
Q

deamination of methyl cytosine produces

A

T mismatched with G

methylation of CpG islands stably silemnce genes (which in this case can cause cancer)

special DNA glycosylase removes T
DNA not very hekpful as only 3% of C nucleotides in uhman feneome are methylated, accounts for 1/3 of all point mutations

5-methyl cytosine is deaminated to thymin

dont understand any of this

56
Q

Benzoapyrene becomes

A

BPDE (burnt meat carcinogen)

57
Q

examples of cross linking agents

A

nitrogen mustard gas, cisplatin, mitomycin C, carmustine (joins Aa to proteins or N)

58
Q

examples of alkylating agents

A

diomethyl sulfate, methyl methamsulfinate

59
Q

intercalating agents

A

ethidum bromide, thalidomide, doxorubicin, daunomycin, intterupts the base pairs

60
Q

Defect: MSH2, 3, 4, MLH1, PMS2

A

colon cancer

mismatch repair

61
Q

defect: Xeroderma pigmentisum, grousp A-G

A

skin cancer, UV sensitivity, neuro issues

nucleoride excision repair

62
Q

defect: ataxia telangeictasia

A

leukeima, lymphoma y ray sensitivity, genomic instabilirt

ATM protein, a protein kinase, activated by DS breaks

63
Q

BRCA 2

A

breast, ovarian, prostate cancer

repair by homologous recombination

64
Q

Fanconi Anemia groups A-G

A

congenital annomalies, leukemia, genome instbaility

cross link repair, DNA interstrand

65
Q

in nucleotide excision repair the distorted adduct undergoes

A

recognition by the NER cpmplex and nicks the DNA on both sides of the damage

if there is a defect here the dz. XP and Cockayne occur

66
Q

in mismatch excision repair for incorect bases in new daughter starnds, MER complex bind to

A

DNA and recognizes mismatch in daighter strand, daigher is cut and segment with mismatch is removed. If this is defective, you will get hereditary nonpolyposis colorecetla cacner

67
Q

Cockayne is a defect in

A

transcription coupled repair

causes growth retrdation, sleletal abnormalities, sensitive to light, RNA polymerase permanently stalled at sites of damage in important genes

68
Q

Rifampcin side effects

A

unregulated hepatic cytochrome P450 enzymes and thus increases in the metabolism of other drugs and hormones by the system

transiently imparts the red color to sweat, tears, etc

69
Q

adopted orphan nuclear receptor superfamily

A

PXR-xenobiotics

70
Q

cytochrome p450 catalyze

A

oxidation reactions

71
Q

hypermethylation

A

dchromsomal instability, loss of imprinting

72
Q

ATG is

A

start of translation (met)

there are 7-% promoters conained within CpG islands proximal to the start of transciprtion (multiple methylated CpG ssites in islands make stabiliy silenced genes)

73
Q

ubiquination and SUMO

A

go toegher to repair damage from stress

SFM Quiz 2 (25 decks)

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