Functions & Dysfunctions of Genomic Regulation Flashcards
Mitotic chromosome are condensed 500 x when compared with interphase chromosomes why?
To prevent physical damage to DNA as chromosomes are separated and passed on to daughter cells
Heirachial organization of DNA
Chromatin= de-condensed nucleosome Nucleosome= histone octomer + DNA
Euchromatin vs Heterochromatin location on chromosome
Position Effect
Euchromatin on 92% of human genome - in middle regions of chromosome Heterochromatin on 8% of human genome - on centrosome and telomeres Position Effect: gene activity depends on position on chromosome ( gene activity will be silenced when closer to heterochromatin)
Information found in Chromosomes (2)
1) Genes ( encoding proteins and RNA molecules)
2) Interspersed DNA that don’t contain genes ( regulatory information or junk DNA)
Important Years of DNA
1909- Wilhelm Johannsen coined “gene”
1953- Watson & Crick described DNA double helix
1966- Nirenberg, Khorana, and Holley determine genetic code
1990- Human Genome Project launched
2001- 90% of human genome
2003/2004- human genome finished
Percentage of DNA sequence in exons
1.5%
CGH Arrays ( Comparative Genome Hybridization)
Scan a person’s DNA along with a normal “reference” DNA
- to detect deletions of genes or copy number variation
RNAi , Long Terminal Repeats (LTRs)
RNAi: miRNA will inhibit gene expression
- hairpin DNA: folded on itself
- Dicer degrades RNA to miRNA
-miRNA bind with protein complex
-miRNA bind to target mRNA and degrade or block translation
LTRs: identical sequences of DNA repeated hundreds of times
- found on proviral DNA (end of retrotransposons)
-formed by reverse transcription of retroviral RNA
ALL introns begins and ends with ?
Begins with […GT]
Ends with [AG…]
Methylation added to which DNA molecule
Cytosine and adenine
- REPRESSES GENE TRANSCRIPTION
(3 Characteristic) Gene Promoter CpG islands
1) acquire abnormal hypermethylation
2) transcriptional silencing
* *3) can be inherited by daughter cells following cell division
DNA polymerase requires primer with ______ to begin processing?
free 3’ OH
SSBP
Single-stranded DNA Binding Protein
- prevent single strand DNA after helicase from binding to itself
- stabilize the unwound DNA
Types of Spontaneous DNA Damage
1) Depurination ( AG)
- cut the adenosine/ guanine off -> base deletion
2) Deamination ( C to U Change, but still bp to G) -> base substitution
Carcinogen effects (well-done steak)
Procarcinogen-> BPDE (carcinogen) EPOXIDE
Metabolism can produce carcinogens -> cause intercalating agents
Types of DNA Repair
1) Polymerase proofreading- check during DNA replication
- mutation 1/ 10^9 or 3, 3 every cellular division
2) direct repair (use light to repair back to normal- photlolyase)
- thymidine dimer
3) base excision repair (takes out only one base)
- one bp mismatch
- depurination
- glycolase, endonuclease, phosphodiesterase, polymerase, ligase
4) nucleotide excision repair (takes out a strand of nucleotides)
- distort shape of DNA
- pyrimidine dimer
- NER complex (nick & endonuclease), HELICASE (unwind strand) polymerase, ligase
5) mismatch repair ( goes on DURING DNA replication in daughter strand)
* *mut S binds
* *Mut L- scans for nicks and degraded the error strand
6) recombination (ONLY DOUBLE STRANDED break)
- ionizing radiation, replication error, oxidizing agent
1. non-homologous end joing- will just degrade regoing that broke and ligase
2. homologous recombination- remove region of messed up nucleotide-> use sister chromatid to look and copy and repair region
Which disease/ disorder to which repair
- Xeroderma pigmentosa= nucleotide excision repair
- Cockayne Syndrome- Transcription Coupled Repair/ NER
- BRCA- Recombination Repair
- Hereditary nonpolysis Colorectal cancer- Mismatch excision Repair
Epigenetics
regulating gene activity independent of DNA sequence that turns genes on or off (depends on development, environmental, aging, diet)
