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MCM I > Functions and Dysfunctions of Genomic Regulation > Flashcards

Functions and Dysfunctions of Genomic Regulation Flashcards

1
Q

snRNA

A

Small nuclear RNA

Packaged with protein to form small nuclear riboproteins (snRNPs) that are part of the spliceosome.

Involved with splicing precursor mRNA and export of mature mRNA

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2
Q

scRNA

A

Small cytoplasmic RNA

Associated with small cytoplasmic ribonucloproteins (scRNPs) involved in protein processing and secretion.

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3
Q

RNase P

A

Ribozyme that cleaves and removes extra RNA sequences in the 5’-leader sequence of precursor tRNA molec.

In Euks, RNase P assists RNA pol III in transcribing noncoding RNAs.

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4
Q

siRNA

A

Short interfering RNA

Short antisense transcript derived from transposons and complementary to certain mRNAs.

siRNA inhibit the translation of target mRNA and enhance their degradation in RNA-inducing silencing complexes.

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5
Q

miRNA

A

Micro RNA involved in posttranscriptional regulation of gene expression

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6
Q

Long Terminal Repeats (LTRs)

A

Identical sequences of DNA
Repeats hundreds/thousands of times
Found at either end of retrotransposons (proviral DNA)
Formed by reverse transcription of retroviral RNA

Used by viruses to insert their genetic material into the host genome

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7
Q

Chromatin

A

Protein + nuclear DNA

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8
Q

Heterochromatin

A

Condensed chromatin
Genetically inactive
Highly concentrated at centromeres and telomeres
Contains few genes
Gene will be silences if relocated near heterochromatin

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9
Q

Euchromatin

A

Less condensed chromatin

Genetically active

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10
Q

Histone positive charge comes from what 2 aa?

A

Lys & Arg

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11
Q

Histone acetylation

A

Keep histone interaction loose (removes (+) charge)

–> More transcription

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12
Q

Histone methylation

A

Keep histone interaction loose (due to physical interference)

–> More transcription

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13
Q

DNA Methylation

A

Physical interference that usually silences transcription and marks certain regions of DNA

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14
Q

HAT

A

Histone acetyltransferase

Acetylates core histones to neutralize (+) lysines to promote chromatin decondensation (make histone with DNA interaction more loose)

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15
Q

HDAC

A

Histone deactylases

Remove acetyl groups from lysines on core histone proteins (restores (+) on lysine so histone can bind to DNA more tightly)

Cancer cells are sensitive to inhibitors of lysine deacetylases

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16
Q

Helicase

A

Unwinds DNA helix

Protein at the replication fork

17
Q

Topisomerase

A

Relieves overwound supercoils
DNA gyrase in bacteria

Every 10bp replicated corresponds to 1 turn
Topoisomerase, breaks a phosphodiester bond to change superhelicity

Inhibitors:
Etoposide (Euk); Flouroquinolones (Prok)

18
Q

Telomerase

A

Fills in telomere gap with hexameric repeats (TTAGGG)

Telomeres shorten after each cell division until eventually cell division stops
Cancer cells have active telomerase activity

19
Q

Spontaneous DNA Damage

A

Lead to either a deletion or a bp substitution in the daughter strand

Depurination- spontaneous rxn –> loss of purine
Spontaneous deamination- C –> U

20
Q

DNA Damage: UV Radiation

A

Forms covalent linkage b/w 2 adjacent pyrimidines
(T-T or C-T)
*Thymine Dimers

21
Q

Methylated Cytosines = Problem, Why?

A

Occurs at Cytosine-phosphate-Guanine (CpG sequences)

Methylation of CpG islands stably silences genes (Cancer/DNA repair genes)

Deamination of methyl-C produces T mismatched with G.
DNA glycosylase recognizes & removes the T
*Repair is relatively ineffective
Only 3% of C nucleotides in human genome are methylated but they account for 1/3 of all point mutations associated with inherited human diseases.

22
Q

Benzopyrenes

A

Adduct formed b/w guanine & BPDE

23
Q

Intercalating agents

A

Ethidium bromide

Thalidomide

24
Q

Base Excision Repair

A

Enzyme involved: DNA glycosylases

Damaged repaired: Single base mismatches (ex. Depurination)

25
Q

Direct repair (enzymatic repair)

A

Damage repaired: Pyrimidine dimer damage, O6-methylguanine

Enzymes involved: DNA photolyase
Methylguanine methyltransferase

26
Q

Nucleotide excision repair

A

Damage repaired: Chemical adducts that distort DNA (ex. pyrimidine dimers, BPDE-guanine adducts, cisplatin adducts)

Enzymes involved: NER protein complex, DNA pol, DNA ligase

Xeroderma pigmentosum

27
Q

Mismatched excision repair

A

Damage repaired: Mismatched base in daughter strand

Enzymes involved: MER complex, helicase/endonuclease, DNA pol delta, DNA ligase

Hereditary nonpolyposis colorectal cancers

28
Q

Recombination repair:

Non-homologous end joining

A

Damage repaired: Double strand breaks, interstrand cross-linking

Mech: Damaged ends filled in and joined; some bases may be missing. Multiple proteins and enzymes including DNA ligase

29
Q

Recombination repair:

Homologous recombination

A

Damage repaired: Double-strand breaks, interstrand cross-linking

Mech: Exonucleases, DNA pol, MER system. Damaged duplex repair using info on undamaged homologous duplex.

BRCA1/2 Breast cancer

30
Q

Transcription-coupled repair

A

Damaged repaired: Stalled RNA pol during transcription (not replication)

Cockayne syndrome

31
Q

Translesion synthesis (bypass synthesis)

A

Damaged repaired: Unrepaired thymine dimers or apurini AP sites

Mech: DNA pol (reduced-fidelity polymerases)

32
Q

Single stranded DNA binding protein

A

Binds the ssDNA that has been separated

33
Q

DNA polymerase alpha

A

Synthesizes RNA-DNA primer

34
Q

DNA polymerase delta and epsilon

A

Synthesize new DNA chain in the 5’–>3’ direction (DNA Pol III in prok)

35
Q

Flap endonuclease 1 (FEN1)

A

Removes RNA primers (DNA Pol I in proks)

36
Q

DNA Pol delta

A

Fills in gaps (DNA Pol I in proks)

37
Q

DNA Ligase

A

Seals nicks

38
Q

Cross-linking and Intercalating

A

Damage by chemical agents; Benzopyrenes

Adduct formed b/w guanine & BPDE (epoxide)

Cross-linking agents: Nitrogen mustard, cisplastin, mitomycin C, carmustine

Alkylating agents: Dimethyl sulfate (DMS), Methyl methansulfonate (MMS)

Intercalating agents: Ethidium bromide, Thalidomide, Doxorubicin, Daunomycin

MCM I (6 decks)

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