kel.1_dna damage response and trancription
TRANSCRIPT
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Presented By:Syayyida Muslimah (1509 100 012)
Dinda Zahidah (1509 100 037)
Wahyu Dewi Iftita (1509 100 707)
Afina Dhuhaini (1510 100 004)
DNA Repair
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DNA is a highly stable molecule that replicates with
amazing accuracy, but changes in DNA structure and
errors of replication do occur.A mutation is defined as an inherited change in genetic
information; the descendants may be cells produced by
cell division or individual organisms produced by
reproduction.
Mutation is the source of all genetic variation, the raw
material of evolution
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Phenotypic Effects of Mutation
Others:
- UV radiation
- Ionizing radiation- Cosmic rays
- X-rays
- Deamination
- Etc.
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Mismatch Repair
Type of damagerepaired :
Replication errors,including mispaired
bases
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Direct Repair
Direct-repair mechanisms do not replace altered
nucleotides but instead change them back into
their original (correct) structures.
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Nucleotide-Excision
RepairRemoves bulky DNAlesions that distort the
double helix, such aspyrimidine dimers orlarge hydrocarbons
attached to the DNA.
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Presented By:
Kelompok 1 : 1. Syayyida Muslimah (1509 100 012)
2. Dinda Zahidah (1509 100 037)
3. Wahyu Dewi Iftita (1509 100 707)
4. Afina Dhuhaini (1510 100 004)
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DNA Damage & Genome Integrity
The mammalian genome is protected against genotoxicinsults by a network of DNA damage response (DDR)
Mechanisms triggered by the detection of DNA lesions
through specific sensors.
The multiprotein nucleotide excision repair (NER)system removes a wide variety of helix-destabilizingDNA lesions including those induced by UV-
irradiation. This broad substrate recognition is achieved by two
distinct subpathways of NER
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Global Genome
NER (GG-NER)
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Processing of
UV-lesions
by TC-NER
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DNA Damage Signaling
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The Replication Stress Response
ATR is the main sensor.
Purposed function : Kinase
activated by blockage of
replication and perhaps
transcription. Roles in normal
replication activation of cell
cycle checkpoints, DNA repair
and apoptosis
The ATR kinase orchestratesDNA repair, apoptosis, S-phase
and G2 arrest via the Chk1, p53
and the Fanconi pathways
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The Transcription Stress Response
SMG1, BRCA1 and ATR
have potensial role in this
stress
The activated SMG1 kinase
could then activate p53 byphosphorylating p53 on the
ser15 site
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The Chromatin Alteration Stress
Response
The ATM kinase may monitor
chromatin alterations
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TC-NER deficiency : human disease
and genome integity
Xeroderma Pigmentosum (XP)
Gejala
- luka terbakar
- banyak bintik-bintik di kulit
- kulit tipis
- mata sensitif pada sinar
matahari
Pengobatan
Belum ditemukan obat untuk
pigmentosum xeroderma.
Tujuan utama dari pengobatanadalah untuk melindungi pasien
dari paparan UV dan dengan
demikian mencegah dampak
buruk itu dapat memiliki pada
kulit.
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Penderita XP sangat sensitif terhadap radiasi ultraviolet (UV), termasuk UVA,UVB, dan UVC. Paparan matahari saja dapat menyebabkan kulit terbakar,kering dan sangat rentan terserang kanker kulit dan melanoma. Selain itu,mata penderita juga sangat sensitif pada cahaya yang juga rentan terserangkanker mata.
Penyebab
cacat dalam mekanisme perbaikan eksisi nukleotida Keterbelakangan mental, sindrom piramidal, neuropathia perifer; lebih parah
sistem saraf pusat (SSP) gangguan diamati ketika mutasi terjadi pada situs DNAXPA
Setelah penyinaran UV pada kultur sel, tidak ada peningkatan kelainankromosom spontan dalam limfosit dari fibroblas, namun setelah paparan UV
naik, trjd peningkatan jumlah pertukaran kromatid saudara (SCE) danpenyimpangan kromosom yang diamati (terutama kromatid-jenis kelainan);fibroblas mengekspresikan kepekaan meningkat menjadi mutagen kimia; tidakada fitur sitogenetika berguna untuk diagnosis XP
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Triochothiodystrophy
Adalah genodermatosis ygditurunkan scr resesif autosomal,ditandai oleh adanya iktiosis,rambut rapuh, penurunan
intelektualitas, postur pendek,mikrosefali, penurunan kesuburan,dan mikrognatia.
Pada TTD dijumpai keadaanfotosensitifitas terhadap sinarmatahari. Adanya defisiensi sulfur
menyebabkan rendahnya kadarsistein dan sistin protein sehinggatrjd iktiosis, rambut dan kuku rapuh.Kelainan kulit tdk berhubungan dgmalignasi seperti XP.
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Any question????
Lets discuss !!!!!
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Question
Sidratu 10-10: Daminasi sitosin
urasil, gambarin donkmbak dinda strukturnya..
Hefdiyah 10-09 : sejauh manakah kerusakan yang tidak
bisa diatasi hingga kemudian muncul berbagai
penyakit??*tergantung dari paparan UV (polutan penyebab
damage) serta protein yg terlibat dalam repaaring
DNA. Jk protein tidak dapat mengatasi maka
terjadilah penyakit tersebut.
Dadang 09-41 : mungkin g sih perubahan spesies
karena perubahan struktur DNA??
*kalo dalam waktu dekat = g mungkin.
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